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1. Transient viral exposure drives functionally-coordinated humoral immune responses in HIV-1 post-treatment controllers

Author: Molinos-Albert, Luis, Lorin, Valerie, Monceaux, Valérie, Orr, Sylvie, Essat, Asma, Dufloo, Jérémy, Schwartz, Olivier, Rouzioux, Christine, Meyer, Laurence, Hocqueloux, Laurent, Sáez-Cirión, Asier, Mouquet, Hugo, Group, Anrs Visconti Study, Prazuck, Thierry, Dieuleveult, Barbara De, Bani-Sadr, Firouzé, Hentzien, Maxime, Berger, Jean-Luc, Kmiec, Isabelle, Pichancourt, Gilles, Nasri, Safa, Hittinger, Gilles, Lambry, Véronique, Beauey, Anne-Cécile, Pialoux, Gilles, Palacios, Christia, Siguier, Martin, Adda, Anne, Foucoin, Jane, Weiss, Laurence, Karmochkine, Marina, Meghadecha, Mohamed, Ptak, Magali, Salmon-Ceron, Dominique, Blanche, Philippe, Piétri, Marie-Pierre, Molina, Jean-Michel, Taulera, Olivier, Lascoux-Combe, Caroline, Ponscarme, Diane, Bertaut, Jeannine Delgado, Makhloufi, Djamila, Godinot, Matthieu, Artizzu, Valérie, Yazdanpanah, Yazdan, Matheron, Sophie, Godard, Cindy, Julia, Zélie, Bernard, Louis, Bastides, Frédéric, Bourgault, Olivier, Jacomet, Christine, Goncalves, Emilie, Meybeck, Agnès, Huleux, Thomas, Cornavin, Pauline, Debab, Yasmine, Théron, David, Miailhes, Patrick, Cotte, Laurent, Pailhes, Sophie, Ogoudjobi, Stanislas, Viard, Jean Paul, Dulucq, Marie-Josée, Bodard, Loïc, Churaqui, Francoise, Guimard, Thomas, Laine, Laetitia, Immunologie humorale - Humoral Immunology, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), HIV, Inflammation et persistance - HIV, Inflammation and Persistence, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Virus et Immunité - Virus and immunity (CNRS-UMR3569), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Service de Microbiologie Clinique [Paris], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), La Source Hospital-CHR, Centre Hospitalier Universitaire de Reims (CHU Reims), Centre Hospitalier Henri Duffaut (Avignon), CHI de Toulon, CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hopital Saint-Louis [AP-HP] (AP-HP), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Hôpital Bretonneau, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand, Centre Hospitalier Gustave Dron [Tourcoing], Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Hôpital de la Croix-Rousse [CHU - HCL], Hôpital Hôtel-Dieu [Paris], Institut mutualiste Monsouris (IMM), Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon (CHD Vendée), We thank the NIH AIDS Reagent Program (Division of AIDS, NIAID, NIH) for contributing to reagents and the Agence National de Recherche sur le SIDA et les hépatites virales (ANRS) for an equipment grant support (AO2013-2 #13553, H.M.). L.M. M-A. is the recipient of a postdoctoral fellowship from the Pasteur-Roux-Cantarini program (Institut Pasteur). H.M. received core grants from the Institut Pasteur, the INSERM and the Milieu Intérieur Program (ANR-10-LABX-69-01). This work was conducted in the context of the ANRS RHIVIERA consortium, and was supported by the ANRS and the NIH/NIAID (grant #: P01AI131365, H.M.)., ANRS VISCONTI Study Group Thierry Prazuck, Barbara De Dieuleveult, Firouzé Bani-Sadr, Maxime Hentzien, Jean-Luc Berger, Isabelle Kmiec, Gilles Pichancourt, Safa Nasri, Gilles Hittinger, Véronique Lambry, Anne-Cécile Beauey, Gilles Pialoux, Christia Palacios, Martin Siguier, Anne Adda, Jane Foucoin, Laurence Weiss, Marina Karmochkine, Mohamed Meghadecha, Magali Ptak, Dominique Salmon-Ceron, Philippe Blanche, Marie-Pierre Piétri, Jean-Michel Molina, Olivier Taulera, Caroline Lascoux-Combe, Diane Ponscarme, Jeannine Delgado Bertaut, Djamila Makhloufi, Matthieu Godinot, Valérie Artizzu, Yazdan Yazdanpanah, Sophie Matheron, Cindy Godard, Zélie Julia, Louis Bernard, Frédéric Bastides, Olivier Bourgault, Christine Jacomet, Emilie Goncalves, Agnès Meybeck, Thomas Huleux, Pauline Cornavin, Yasmine Debab, David Théron, Patrick Miailhes, Laurent Cotte, Sophie Pailhes, Stanislas Ogoudjobi, Jean Paul Viard, Marie-Josée Dulucq, Loïc Bodard, Francoise Churaqui, Thomas Guimard & Laetitia Laine, ANR-10-LABX-0069,MILIEU INTERIEUR,GENETIC & ENVIRONMENTAL CONTROL OF IMMUNE PHENOTYPE VARIANCE: ESTABLISHING A PATH TOWARDS PERSONALIZED MEDICINE(2010), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC), Institut Pasteur [Paris]-Université Paris Cité (UPC), Virus et Immunité - Virus and immunity, and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPC)
Subjects: Multidisciplinary, MESH: Humans, General Physics and Astronomy, HIV Infections, General Chemistry, MESH: HIV Infections, Antibodies, Neutralizing, General Biochemistry, Genetics and Molecular Biology, Immunity, Humoral, MESH: Antibodies, Neutralizing, MESH: HIV-1, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, HIV-1, Humans, Viremia, MESH: Immunity, Humoral, MESH: Viremia
Abstract: HIV-1 post-treatment controllers are rare individuals controlling HIV-1 infection for years after antiretroviral therapy interruption. Identification of immune correlates of control in post-treatment controllers could aid in designing effective HIV-1 vaccine and remission strategies. Here, we perform comprehensive immunoprofiling of the humoral response to HIV-1 in long-term post-treatment controllers. Global multivariate analyses combining clinico-virological and humoral immune data reveal distinct profiles in post-treatment controllers experiencing transient viremic episodes off therapy compared to those stably aviremic. Virally-exposed post-treatment controllers display stronger HIV-1 humoral responses, and develop more frequently Env-specific memory B cells and cross-neutralizing antibodies. Both are linked to short viremic exposures, which are also accompanied by an increase in blood atypical memory B cells and activated subsets of circulating follicular helper T cells. Still, most humoral immune variables only correlate with Th2-like circulating follicular helper T cells. Thus, post-treatment controllers form a heterogeneous group with two distinct viral behaviours and associated immune signatures. Post-treatment controllers stably aviremic present “silent” humoral profiles, while those virally-exposed develop functionally robust HIV-specific B-cell and antibody responses, which may participate in controlling infection.
Published: 2022
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2. Broadly neutralizing anti-HIV-1 antibodies tether viral particles at the surface of infected cells

Author: Jérémy Dufloo, Cyril Planchais, Stéphane Frémont, Valérie Lorin, Florence Guivel-Benhassine, Karl Stefic, Nicoletta Casartelli, Arnaud Echard, Philippe Roingeard, Hugo Mouquet, Olivier Schwartz, Timothée Bruel, Virus et Immunité - Virus and immunity (CNRS-UMR3569), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), École Doctorale Bio Sorbonne Paris Cité [Paris] (ED562 - BioSPC), Université Sorbonne Paris Cité (USPC)-Université Paris Cité (UPCité), Immunologie humorale - Humoral Immunology, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Trafic membranaire et Division cellulaire - Membrane Traffic and Cell Division, Hôpital Bretonneau, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Plateforme IBISA de Microscopie Electronique [CHRU de Tours] (UNIV Tours), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Université de Tours (UT), Vaccine Research Institute [Créteil, France] (VRI), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), O.S. is funded by Institut Pasteur, Agence Nationale de Recherches sur le Sida et les Hépatites Virales (ANRS), Sidaction, the Vaccine Research Institute (ANR-10-LABX-77), Labex IBEID (ANR-10-LABX-62-IBEID), 'TIMTAMDEN' ANR-14-CE14-0029, 'CHIKV-Viro-Immuno' ANR-14-CE14-0015-01, and the Gilead HIV cure program. J.D. is funded by a Ph.D grant from the French Ministry of Higher Education and Research. H.M. is funded by the Institut Pasteur, the Milieu Intérieur Program (ANR-10-LABX-69-01), INSERM, ANRS, and Gilead HIV cure program. C.P. was supported by an ANRS fellowship. A.E. and S.F. are funded by Institut Pasteur, CNRS, and ANRS (ANRS-21020 AP2020-2). P.R. is funded by INSERM, Université de Tours and ANRS., ANR-10-LABX-0077,VRI,Initiative for the creation of a Vaccine Research Institute(2010), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-14-CE14-0029,TIMTAMDEN,Rôle des récepteurs TIM et TAM dans l'infection des cellules cibles par le virus de la dengue(2014), ANR-14-CE14-0015,CHIKV-Viro-Immuno,Multiplication et Relation avec l'hôte du virus Chikungunya(2014), ANR-10-LABX-0069,MILIEU INTERIEUR,GENETIC & ENVIRONMENTAL CONTROL OF IMMUNE PHENOTYPE VARIANCE: ESTABLISHING A PATH TOWARDS PERSONALIZED MEDICINE(2010), Virus et Immunité - Virus and immunity, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Vaccine Research Institute (VRI), Institut Pasteur, Agence Nationale de la Recherche (France), Ministére de l'Education Nationale de la Recherche et de la Technologie (France), and Université de Tours
Subjects: MESH: Epitopes, T-Lymphocytes, Science, viruses, General Physics and Astronomy, HIV Infections, MESH: Host Microbial Interactions, HIV Antibodies, General Biochemistry, Genetics and Molecular Biology, Cell Line, MESH: Antibodies, Neutralizing, MESH: HIV-1, Epitopes, MESH: Antibody-Dependent Cell Cytotoxicity, Humans, MESH: Broadly Neutralizing Antibodies, Multidisciplinary, MESH: Humans, Host Microbial Interactions, MESH: HIV Antibodies, Antibody-Dependent Cell Cytotoxicity, Virion, env Gene Products, Human Immunodeficiency Virus, virus diseases, General Chemistry, MESH: HIV Infections, Antibodies, Neutralizing, MESH: Cell Line, MESH: T-Lymphocytes, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, HIV-1, MESH: Virion, MESH: env Gene Products, Human Immunodeficiency Virus, Broadly Neutralizing Antibodies
Abstract: Broadly neutralizing antibodies (bNAbs) targeting the HIV-1 envelope glycoprotein (Env) are promising molecules for therapeutic or prophylactic interventions. Beyond neutralization, bNAbs exert Fc-dependent functions including antibody-dependent cellular cytotoxicity and activation of the complement. Here, we show that a subset of bNAbs targeting the CD4 binding site and the V1/V2 or V3 loops inhibit viral release from infected cells. We combined immunofluorescence, scanning electron microscopy, transmission electron microscopy and immunogold staining to reveal that some bNAbs form large aggregates of virions at the surface of infected cells. This activity correlates with the capacity of bNAbs to bind to Env at the cell surface and to neutralize cell-free viral particles. We further show that antibody bivalency is required for viral retention, and that aggregated virions are neutralized. We have thus identified an additional antiviral activity of bNAbs, which block HIV-1 release by tethering viral particles at the surface of infected cells., O.S. is funded by Institut Pasteur, Agence Nationale de Recherches sur le Sida et les Hépatites Virales (ANRS), Sidaction, the Vaccine Research Institute (ANR-10-LABX-77), Labex IBEID (ANR-10-LABX-62-IBEID), “TIMTAMDEN” ANR-14-CE14-0029, “CHIKV-Viro-Immuno” ANR-14-CE14-0015-01, and the Gilead HIV cure program. J.D. is funded by a Ph.D grant from the French Ministry of Higher Education and Research. H.M. is funded by the Institut Pasteur, the Milieu Intérieur Program (ANR-10-LABX-69-01), INSERM, ANRS, and Gilead HIV cure program. C.P. was supported by an ANRS fellowship. A.E. and S.F. are funded by Institut Pasteur, CNRS, and ANRS (ANRS-21020 AP2020-2). P.R. is funded by INSERM, Université de Tours and ANRS.
Published: 2022
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3. Phagocytosis by an HIV antibody is associated with reduced viremia irrespective of enhanced complement lysis

Author: David A. Spencer, Benjamin S. Goldberg, Shilpi Pandey, Tracy Ordonez, Jérémy Dufloo, Philip Barnette, William F. Sutton, Heidi Henderson, Rebecca Agnor, Lina Gao, Timothée Bruel, Olivier Schwartz, Nancy L. Haigwood, Margaret E. Ackerman, Ann J. Hessell, Oregon National Primate Research Center (ONPRC), Oregon Health and Science University [Portland] (OHSU), Dartmouth College [Hanover], Virus et Immunité - Virus and immunity (CNRS-UMR3569), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), École Doctorale Bio Sorbonne Paris Cité [Paris] (ED562 - BioSPC), Université Sorbonne Paris Cité (USPC)-Université Paris Cité (UPCité), Vaccine Research Institute [Créteil, France] (VRI), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), This work was supported by the following grants: R01 AI129801 (A.J.H.), P51 OD011092, and U42 OD023038-03, We thank Diane Kubitz and Jonathan Otsuji at The Scripps Research Institute Antibody Production Core facility for antibody production, Christina Corbaci for assistance with figure design and production, David Evans for providing the CD4+CCR5+ NKR24 and KHYG-1 NK cell lines, and the NIH/NIAID Vaccine Research Center for the expression plasmid for 10E8v4 and the anti-10E8 mAb 2D1. We acknowledge the NIH AIDS Reagent Program for providing the following reagents: anti-HIV-1 Env mAb b12 (ARP-2640), TZM-bl cells with FcRs (ARP-11796, ARP-11797, ARP-11798), SIVmac239 gag pooled peptides (ARP-12364), and SHIVSF162P3 virus stock (ARP-6526)., Virus et Immunité - Virus and immunity, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), and Vaccine Research Institute (VRI)
Subjects: Male, Science, Simian Acquired Immunodeficiency Syndrome, General Physics and Astronomy, HIV Infections, HIV Antibodies, General Biochemistry, Genetics and Molecular Biology, Phagocytosis, Cell Line, Tumor, Animals, Humans, Viremia, Multidisciplinary, Antibody-Dependent Cell Cytotoxicity, virus diseases, Complement System Proteins, General Chemistry, Macaca mulatta, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, HIV-1, Leukocytes, Mononuclear, Cytokines, Female, Simian Immunodeficiency Virus, Broadly Neutralizing Antibodies
Abstract: Increasingly, antibodies are being used to treat and prevent viral infections. In the context of HIV, efficacy is primarily attributed to dose-dependent neutralization potency and to a lesser extent Fc-mediated effector functions. It remains unclear whether augmenting effector functions of broadly neutralizing antibodies (bNAbs) may improve their clinical potential. Here, we use bNAb 10E8v4 targeting the membrane external proximal region (MPER) to examine the role of antibody-mediated effector and complement (C’) activity when administered prophylactically against SHIV challenge in rhesus macaques. With sub-protective dosing, we find a 78–88% reduction in post-acute viremia that is associated with 10E8v4-mediated phagocytosis acting at the time of challenge. Neither plasma nor tissue viremic outcomes in vivo is improved with an Fc-modified variant of 10E8v4 enhanced for C’ functions as determined in vitro. These results suggest that effector functions inherent to unmodified 10E8v4 contribute to efficacy against SHIVSF162P3 in the absence of plasma neutralizing titers, while C’ functions are dispensable in this setting, informing design of bNAb modifications for improving protective efficacy., This work was supported by the following grants: R01 AI129801 (A.J.H.), P51 OD011092, and U42 OD023038-03.
Published: 2022
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4. Reduced sensitivity of SARS-CoV-2 variant Delta to antibody neutralization

Author: Najiby Kassis-Chikhani, Samira Fafi-Kremer, Olivier Schwartz, Laurent Bélec, Matthieu Prot, Cyril Planchais, Timothée Bruel, Laura Courtellemont, Florence Guivel-Benhassine, Artem Baidaliuk, Isabelle Staropoli, Julien Le Guen, Etienne Simon-Loriere, Laurent Hocqueloux, Delphine Planas, David Veyer, Pierre Gantner, Maaran Michael Rajah, Aurélie Velay, Thierry Prazuck, Dhiaeddine Edriss, Félix A. Rey, Françoise Porrot, Hélène Péré, Floriane Gallais, Aymeric Sève, Nicolas Robillard, Julien Puech, Hugo Mouquet, Virus et Immunité - Virus and immunity (CNRS-UMR3569), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Vaccine Research Institute [Créteil, France] (VRI), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Génomique fonctionnelle des tumeurs solides = Functional Genomics of Solid Tumors [CRC] (FunGeST), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Génomique évolutive des virus à ARN - Evolutionary genomics of RNA viruses, Institut Pasteur [Paris] (IP), Université Paris Cité (UPCité), Immunologie humorale - Humoral Immunology, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Strasbourg, Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional d'Orléans (CHRO), Virologie Structurale - Structural Virology, The Opera system was co-funded by the Institut Pasteur and the Région Île de France (DIM1Health). Work in the O.S. laboratory is funded by the Institut Pasteur, Urgence COVID-19 Fundraising Campaign of Institut Pasteur, Fondation pour la Recherche Médicale (FRM), ANRS, the Vaccine Research Institute (ANR-10-LABX-77), Labex IBEID (ANR-10-LABX-62-IBEID), ANR/FRM Flash Covid PROTEO-SARS-CoV-2 and IDISCOVR. Work in UPBI is funded by grant ANR-10-INSB-04-01 and the Région Île-de-France program DIM1-Health. D.P. is supported by the Vaccine Research Institute. The H.M. laboratory is funded by the Institut Pasteur, the Milieu Intérieur Program (ANR-10-LABX-69-01), INSERM, REACTing, EU (RECOVER) and Fondation de France (00106077) grants. The S.F.K. laboratory is funded by Strasbourg University Hospitals (SeroCoV-HUS, PRI 7782), the Programme Hospitalier de Recherche Clinique (PHRC N 2017–HUS no. 6997), the Agence Nationale de la Recherche (ANR-18-CE17-0028), Laboratoire d’Excellence TRANSPLANTEX (ANR-11-LABX-0070_TRANSPLANTEX) and the Institut National de la Santé et de la Recherche Médicale (UMR_S 1109). The E.S.-L. laboratory is funded by the Institut Pasteur and the French Government’s Investissement d’Avenir programme, Laboratoire d’Excellence ‘Integrative Biology of Emerging Infectious Diseases’ (grant no. ANR-10-LABX-62-IBEID)., We thank N. Casartelli for critical reading of the manuscript, P. Guardado Calvo for discussion, the individuals who participated in the study, members of the Virus and Immunity Unit for discussions and help, N. Aulner and the UTechS Photonic BioImaging (UPBI) core facility (Institut Pasteur), a member of the France BioImaging network, for image acquisition and analysis, and the DRCI, CIC, Médecine du Travail and Pôle de Biologie teams (CHU de Strasbourg) for the management of the Strasbourg cohort and serology testing., ANR-10-LABX-0077,VRI,Initiative for the creation of a Vaccine Research Institute(2010), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-20-COVI-0059,PROTEO-SARS-CoV-2,Protéomique du SARS-CoV-2(2020), ANR-10-INBS-0004,France-BioImaging,Développment d'une infrastructure française distribuée coordonnée(2010), ANR-10-LABX-0069,MILIEU INTERIEUR,GENETIC & ENVIRONMENTAL CONTROL OF IMMUNE PHENOTYPE VARIANCE: ESTABLISHING A PATH TOWARDS PERSONALIZED MEDICINE(2010), ANR-18-CE17-0028,HuMABK,Les anticorps monoclonaux humains : une Nouvelle approche thérapeutique contre l'infection par le virus BK et les maladies associées(2018), ANR-11-LABX-0070,TRANSPLANTEX,Nouveaux loci d'histocompatibilité/biomarqueurs en transplantation humaine: de la découverte à l'app(2011), European Project: 101003589, H2020-SC1-PHE-CORONAVIRUS-2020,RECOVER(2020), Virus et Immunité - Virus and immunity, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Vaccine Research Institute (VRI), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)-École pratique des hautes études (EPHE), Institut Pasteur [Paris], Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPC)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPC), and Université Paris Cité (UPC)
Subjects: Male, Delta, COVID-19 Vaccines, medicine.drug_class, India, Alpha (ethology), Biology, Antibodies, Monoclonal, Humanized, Antibodies, Viral, Monoclonal antibody, Neutralization, Epitope, Epitopes, Immune system, Neutralization Tests, medicine, Humans, Immune Evasion, Multidisciplinary, COVID-19, Convalescence, Middle Aged, Antibodies, Neutralizing, Virology, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Spike Glycoprotein, Coronavirus, Monoclonal, biology.protein, France, Antibody
Abstract: The SARS-CoV-2 B.1.617 lineage was identified in October 2020 in India1–5. Since then, it has become dominant in some regions of India and in the UK, and has spread to many other countries6. The lineage includes three main subtypes (B1.617.1, B.1.617.2 and B.1.617.3), which contain diverse mutations in the N-terminal domain (NTD) and the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein that may increase the immune evasion potential of these variants. B.1.617.2—also termed the Delta variant—is believed to spread faster than other variants. Here we isolated an infectious strain of the Delta variant from an individual with COVID-19 who had returned to France from India. We examined the sensitivity of this strain to monoclonal antibodies and to antibodies present in sera from individuals who had recovered from COVID-19 (hereafter referred to as convalescent individuals) or who had received a COVID-19 vaccine, and then compared this strain with other strains of SARS-CoV-2. The Delta variant was resistant to neutralization by some anti-NTD and anti-RBD monoclonal antibodies, including bamlanivimab, and these antibodies showed impaired binding to the spike protein. Sera collected from convalescent individuals up to 12 months after the onset of symptoms were fourfold less potent against the Delta variant relative to the Alpha variant (B.1.1.7). Sera from individuals who had received one dose of the Pfizer or the AstraZeneca vaccine had a barely discernible inhibitory effect on the Delta variant. Administration of two doses of the vaccine generated a neutralizing response in 95% of individuals, with titres three- to fivefold lower against the Delta variant than against the Alpha variant. Thus, the spread of the Delta variant is associated with an escape from antibodies that target non-RBD and RBD epitopes of the spike protein. The SARS-CoV-2 Delta variant partially evades neutralization by several monoclonal antibodies and by sera from individuals who have had COVID-19, but two doses of anti-COVID-19 vaccines still generate a strong neutralizing response.
Published: 2021
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5. Human Claudin-Derived Peptides Block the Membrane Fusion Process of Zika Virus and Are Broad Flavivirus Inhibitors

Author: Jim Zoladek, Julien Burlaud-Gaillard, Maxime Chazal, Sophie Desgraupes, Patricia Jeannin, Antoine Gessain, Nathalie Pardigon, Mathieu Hubert, Philippe Roingeard, Nolwenn Jouvenet, Philippe V. Afonso, Institut Pasteur [Paris] (IP), Université Paris Cité (UPCité), Epidémiologie et Physiopathologie des Virus Oncogènes / Oncogenic Virus Epidemiology and Pathophysiology (EPVO (UMR_3569 / U-Pasteur_3)), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Université de Tours (UT), Morphogénèse et antigénicité du VIH et du virus des Hépatites (MAVIVH - U1259 Inserm - CHRU Tours ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Virologie (CNRS - UMR3569), Signalisation antivirale - Virus sensing and signaling, Environnement et Risques infectieux - Environment and Infectious Risks (ERI), Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Virus et Immunité - Virus and immunity, This work was supported by a Pasteur-Fiocruz grant and the 'Investissement d’Avenir' as part of a 'Laboratoire d’Excellence' (LabEx) French research program: Integrative Biology of Emerging Infectious Diseases (ANR10-LBX-62 IBEID). Jim Zoladek and Sophie Desgraupes were the recipients of Ph.D. fellowships from the ED562-BioSPC and the French ministry of education and research., We thank Nicoletta Casartelli for her help on HIV-1-related experiments. We thank Florence Guivel-Benhassine for help with virus titration, Charlotte Calvet for help with sample preparation for scanning electron microscopy, Sylvie Van der Werf for the SARS-CoV-2 isolate used in this study, and Nicolas Escriou for the gift of a SARS-CoV-2 spike antibody. We thank Stéphane Roche for his biochemistry-related input and discussions on the project. We thank Pierre-Emmanuel Ceccaldi for his input and discussions on the project., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), Afonso, Philippe, Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - VALID, Virologie (CNRS-UMR3569), and Virus et Immunité - Virus and immunity (CNRS-UMR3569)
Subjects: Microbiology (medical), [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, General Immunology and Microbiology, Ecology, Physiology, Zika Virus Infection, flavivirus, Cell Biology, Zika Virus, Antiviral Agents, Lipids, Membrane Fusion, antimicrobial peptides, Infectious Diseases, Zika, Claudin-1, Claudins, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Genetics, claudin, Humans, Peptides
Abstract: International audience; Zika virus (ZIKV) is a mosquito-borne flavivirus that emerged in the Pacific islands in 2007 and spread to the Americas in 2015. The infection remains asymptomatic in most cases but can be associated with severe neurological disorders. Despite massive efforts, no specific drug or vaccine against ZIKV infection is available to date. Claudins are tight-junction proteins that favor the entry of several flaviviruses, including ZIKV. In this study, we identified two peptides derived from the N-terminal sequences of claudin-7 and claudin-1, named CL7.1 and CL1.1, respectively, that inhibited ZIKV infection in a panel of human cell lines. Using cell-to-cell fusion assays, we demonstrated that these peptides blocked the ZIKV E-mediated membrane fusion. A comparison of the antiviral efficacy of CL1.1 and CL7.1 pointed to the importance of the peptide amphipathicity. Electron microscopic analysis revealed that CL1.1 altered the ultrastructure of the viral particles likely by binding the virus lipid envelope. However, amphipathicity could not fully explain the antiviral activity of CL1.1. In silico docking simulations suggested that CL1.1 may also interact with the E protein, near its stem region. Overall, our data suggested that claudin-derived peptides inhibition may be linked to simultaneous interaction with the E protein and the viral lipid envelope. Finally, we found that CL1.1 also blocked infection by yellow fever and Japanese encephalitis viruses but not by HIV-1 or SARS-CoV-2. Our results provide a basis for the future development of therapeutics against a wide range of endemic and emerging flaviviruses. IMPORTANCE Zika virus (ZIKV) is a flavivirus transmitted by mosquito bites that have spread to the Pacific Islands and the Americas over the past decade. The infection remains asymptomatic in most cases but can cause severe neurological disorders. ZIKV is a major public health threat in areas of endemicity, and there is currently no specific antiviral drug or vaccine available. We identified two antiviral peptides deriving from the N-terminal sequences of claudin-7 and claudin-1 with the latter being the most effective. These peptides block the envelope-mediated membrane fusion. Our data suggested that the inhibition was likely achieved by simultaneously interacting with the viral lipid envelope and the E protein. The peptides also inhibited other flaviviruses. These results could provide the basis for the development of therapies that might target a wide array of flaviviruses from current epidemics and possibly future emergences.
Published: 2022
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6. Species-Specific Molecular Barriers to SARS-CoV-2 Replication in Bat Cells

Author: Sophie-Marie Aicher, Felix Streicher, Maxime Chazal, Delphine Planas, Dongsheng Luo, Julian Buchrieser, Monika Nemcova, Veronika Seidlova, Jan Zukal, Jordi Serra-Cobo, Dominique Pontier, Bertrand Pain, Gert Zimmer, Olivier Schwartz, Philippe Roingeard, Jiri Pikula, Laurent Dacheux, Nolwenn Jouvenet, Signalisation antivirale - Virus sensing and signaling, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Vaccine Research Institute (VRI), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Virus et Immunité - Virus and immunity, Lyssavirus, épidémiologie et neuropathologie - Lyssavirus Epidemiology and Neuropathology, Institut Pasteur [Paris]-Université Paris Cité (UPCité), University of Veterinary and Pharmaceutical Sciences [Brno] (VFU), Universitat de Barcelona (UB), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Institut cellule souche et cerveau / Stem Cell and Brain Research Institute (U1208 Inserm - UCBL1 / SBRI - USC 1361 INRAE), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), University of Bern, Institute of Virology and Immunology [Mittelhäusern] (IVI), Morphogénèse et antigénicité du VIH et du virus des Hépatites (MAVIVH - U1259 Inserm - CHRU Tours ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), This study was funded by the CNRS (N.J. and O.S.), Institut Pasteur (N.J., L.D., and O.S.), the 'Urgence COVID-19' fundraising campaign of Institut Pasteur (N.J., L.D., and O.S.), the University of Veterinary Sciences Brno (FVHE/Pikula/ITA2021) (J.P.), the FINOVI Fondation (AO13) and Covid IDEX Universite Lyon 1 (B.P.), LabEx Ecofect (ANR-11-LABX-0048) (Do.P.), Labex IBEID (ANR-10-LABX-62-IBEID) (O.S.), ANR/FRM Flash Covid PROTEO-SARS-CoV-2 (O.S.), and IDISCOVR (O.S.). S.-M.A. and De.P. are supported by the Pasteur-Paris University International Ph.D. Program and the Vaccine Research Institute (ANR-10-LABX-77), respectively. D.L. was funded by the Chinese Scholarship Council and Institut Pasteur. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript., ANR-11-LABX-0048,ECOFECT,Dynamiques eco-évolutives des maladies infectieuses(2011), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-10-LABX-0077,VRI,Initiative for the creation of a Vaccine Research Institute(2010), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Virus et Immunité - Virus and immunity (CNRS-UMR3569), Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Institut cellule souche et cerveau / Stem Cell and Brain Research Institute (SBRI), Girard, Agnès, Dynamiques eco-évolutives des maladies infectieuses - - ECOFECT2011 - ANR-11-LABX-0048 - LABX - VALID, Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - VALID, Laboratoires d'excellence - Initiative for the creation of a Vaccine Research Institute - - VRI2010 - ANR-10-LABX-0077 - LABX - VALID, and Vaccine Research Institute [Créteil, France] (VRI)
Subjects: [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, 630 Agriculture, SARS-CoV-2, Immunology, coronavirus, Virus Replication, Microbiology, Species Specificity, Virology, Insect Science, Chiroptera, bat cells, Spike Glycoprotein, Coronavirus, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Animals, Humans, Receptors, Virus, Angiotensin-Converting Enzyme 2, innate immunity
Abstract: Bats are natural reservoirs of numerous coronaviruses, including the potential ancestor of SARS-CoV-2. Knowledge concerning the interaction between coronaviruses and bat cells is sparse. We investigated the ability of primary cells from Rhinolophus and Myotis species, as well as of established and novel cell lines from Myotis myotis, Eptesicus serotinus, Tadarida brasiliensis, and Nyctalus noctula, to support SARS-CoV-2 replication. None of these cells were permissive to infection, not even the ones expressing detectable levels of angiotensin-converting enzyme 2 (ACE2), which serves as the viral receptor in many mammalian species. The resistance to infection was overcome by expression of human ACE2 (hACE2) in three cell lines, suggesting that the restriction to viral replication was due to a low expression of bat ACE2 (bACE2) or the absence of bACE2 binding in these cells. Infectious virions were produced but not released from hACE2-transduced M. myotis brain cells. E. serotinus brain cells and M. myotis nasal epithelial cells expressing hACE2 efficiently controlled viral replication, which correlated with a potent interferon response. Our data highlight the existence of species-specific and cell-specific molecular barriers to viral replication in bat cells. These novel chiropteran cellular models are valuable tools to investigate the evolutionary relationships between bats and coronaviruses. IMPORTANCE Bats are host ancestors of several viruses that cause serious disease in humans, as illustrated by the ongoing SARS-CoV-2 pandemic. Progress in investigating bat-virus interactions has been hampered by a limited number of available bat cellular models. We have generated primary cells and cell lines from several bat species that are relevant for coronavirus research. The various permissivities of the cells to SARS-CoV-2 infection offered the opportunity to uncover some species-specific molecular restrictions to viral replication. All bat cells exhibited a potent entry-dependent restriction. Once this block was overcome by overexpression of human ACE2, which serves at the viral receptor, two bat cell lines controlled well viral replication, which correlated with the inability of the virus to counteract antiviral responses. Other cells potently inhibited viral release. Our novel bat cellular models contribute to a better understanding of the molecular interplays between bat cells and viruses.
Published: 2022
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7. Tracking receptor motions at the plasma membrane reveals distinct effects of ligands on CCR5 dynamics depending on its dimerization status

Author: Fanny Momboisse, Giacomo Nardi, Philippe Colin, Melanie Hery, Nelia Cordeiro, Simon Blachier, Olivier Schwartz, Fernando Arenzana-Seisdedos, Nathalie Sauvonnet, Jean-Christophe Olivo-Marin, Bernard Lagane, Thibault Lagache, Anne Brelot, Virus et Immunité - Virus and immunity (CNRS-UMR3569), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Analyse d'images biologiques - Biological Image Analysis (BIA), Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Dynamique des Interactions Hôte-Pathogène - Dynamics of Host-Pathogen Interactions, Pathogénie Virale - Viral Pathogenesis, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de Biologie cellulaire et infection - Department of Cell Biology and infection (BCI), Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), This work was supported by grants from Agence National de Recherche sur le SIDA et les hepatitis virales (ANRS), the French Government’s Investissement d’Avenir program, Laboratoire d’excellence 'Integrative Biology of Emerging Infectious Diseases’ (grant ANR-10-LABX-62- IBEID), INCEPTION (ANR-16-CONV-0005) and GET-REDI (ANR-21-CE44-0030). UTechS PBI is part of theFrance–BioImaging infrastructure network (FBI) supported by the French National Research Agency (ANR-10- INBS- 04, Investments for the Future), and acknowledges support from Institut Pasteur, ANR/ FBI, the Région Ile-de- France (program ‘Domaine d'Intérêt Majeur-Malinf’ and DIM1HEALTH), and the French Government Investissement d'Avenir Programme—Laboratoire d'Excellence ‘Integrative Biology of Emerging Infectious Diseases’ (ANR-10-LABX-62-IBEID) for the use of ELYRA PS1 LSM780and ELYRA7 microscopes. FM was the recipient of ANR-10-LABX-62-IBEID fellowship, GN of INCEPTION (ANR-16- CONV-0005) fellowship and PC of an ANRS fellowship, ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-16-CONV-0005,INCEPTION,Institut Convergences pour l'étude de l'Emergence des Pathologies au Travers des Individus et des populatiONs(2016), ANR-21-CE44-0030,GET-REDI,Cibler la dimérisation des récepteurs de chimiokines CCR2 et CCR5: vers une meilleure régulation de l'inflammation(2021), ANR-10-INBS-0004,France-BioImaging,Développment d'une infrastructure française distribuée coordonnée(2010), Virus et Immunité - Virus and immunity, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Brelot, Anne, Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - VALID, Institut Convergences pour l'étude de l'Emergence des Pathologies au Travers des Individus et des populatiONs - - INCEPTION2016 - ANR-16-CONV-0005 - CONV - VALID, Cibler la dimérisation des récepteurs de chimiokines CCR2 et CCR5: vers une meilleure régulation de l'inflammation - - GET-REDI2021 - ANR-21-CE44-0030 - AAPG2021 - VALID, and Développment d'une infrastructure française distribuée coordonnée - - France-BioImaging2010 - ANR-10-INBS-0004 - INBS - VALID
Subjects: Receptors, CCR5, General Immunology and Microbiology, none, single-particle-tracking, [SDV]Life Sciences [q-bio], General Neuroscience, Cell Membrane, chemokine receptor, imaging, General Medicine, Ligands, General Biochemistry, Genetics and Molecular Biology, Receptors, G-Protein-Coupled, [SDV] Life Sciences [q-bio], GPCR, statistics, cell biology, physics of living systems, HIV-1, Humans, Protein Multimerization, CCR5, Dimerization
Abstract: International audience; G-protein-coupled receptors (GPCR) are present at the cell surface in different conformational and oligomeric states. However, how these states impact GPCRs biological function and therapeutic targeting remains incompletely known. Here, we investigated this issue in living cells for the CC chemokine receptor 5 (CCR5), a major receptor in inflammation and the principal entry co-receptor for Human Immunodeficiency Viruses type 1 (HIV-1). We used TIRF microscopy and a statistical method to track and classify the motion of different receptor subpopulations. We showed a diversity of ligand-free forms of CCR5 at the cell surface constituted of various oligomeric states and exhibiting transient Brownian and restricted motions. These forms were stabilized differently by distinct ligands. In particular, agonist stimulation restricted the mobility of CCR5 and led to its clustering, a feature depending on β-arrestin, while inverse agonist stimulation exhibited the opposite effect. These results suggest a link between receptor activation and immobilization. Applied to HIV-1 envelope glycoproteins gp120, our quantitative analysis revealed agonist-like properties of gp120s. Distinct gp120s influenced CCR5 dynamics differently, suggesting that they stabilize different CCR5 conformations. Then, using a dimerization-compromized mutant, we showed that dimerization (i) impacts CCR5 precoupling to G proteins, (ii) is a pre-requisite for the immobilization and clustering of receptors upon activation, and (iii) regulates receptor endocytosis, thereby impacting the fate of activated receptors. This study demonstrates that tracking the dynamic behavior of a GPCR is an efficient way to link GPCR conformations to their functions, therefore improving the development of drugs targeting specific receptor conformations.
Published: 2022
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8. Potent human broadly SARS-CoV-2–neutralizing IgA and IgG antibodies effective against Omicron BA.1 and BA.2

Author: Planchais, Cyril, Fernández, Ignacio, Bruel, Timothée, de Melo, Guilherme, Prot, Matthieu, Beretta, Maxime, Guardado-Calvo, Pablo, Dufloo, Jérémy, Molinos-Albert, Luis, Backovic, Marija, Chiaravalli, Jeanne, Giraud, Emilie, Vesin, Benjamin, Conquet, Laurine, Grzelak, Ludivine, Planas, Delphine, Staropoli, Isabelle, Guivel-Benhassine, Florence, Hieu, Thierry, Boullé, Mikaël, Cervantes-Gonzalez, Minerva, Ungeheuer, Marie-Noëlle, Charneau, Pierre, van der Werf, Sylvie, Agou, Fabrice, Bartoli, Marie, Diallo, Alpha, Le Mestre, Soizic, Paul, Christelle, Petrov-Sanchez, Ventzislava, Yazdanpanah, Yazdan, Ficko, Cécile, Chirouze, Catherine, Andrejak, Claire, Malvy, Denis, Goehringer, François, Rossignol, Patrick, Gigante, Tristan, Gilg, Morgane, Rossignol, Bénédicte, Etienne, Manuel, Beluze, Marine, Bachelet, Delphine, Bhavsar, Krishna, Bouadma, Lila, Chair, Anissa, Charpentier, Charlotte, Chenard, Léo, Couffignal, Camille, Debray, Marie-Pierre, Descamps, Diane, Duval, Xavier, Eloy, Philippine, Esposito-Farese, Marina, Florence, Aline-Marie, Ghosn, Jade, Hoffmann, Isabelle, Kafif, Ouifiya, Khalil, Antoine, Lafhej, Nadhem, Laouénan, Cédric, Laribi, Samira, Le, Minh, Le Hingrat, Quentin, Letrou, Sophie, Mentré, France, Peytavin, Gilles, Piquard, Valentine, Roy, Carine, Schneider, Marion, Su, Richa, Tardivon, Coralie, Timsit, Jean-François, Tubiana, Sarah, Visseaux, Benoît, Deplanque, Dominique, Hulot, Jean-Sébastien, Diehl, Jean-Luc, Picone, Olivier, Angoulvant, François, Abrous, Amal, Couffin-Cadiergues, Sandrine, da Silva, Fernanda, Esperou, Hélène, Houas, Ikram, Jaafoura, Salma, Papadopoulos, Aurélie, Gaymard, Alexandre, Lina, Bruno, Rosa-Calatrava, Manuel, Dorival, Céline, Guedj, Jérémie, Lingas, Guillaume, Neant, Nadège, Abel, Laurent, Manda, Victoria, Behillil, Sylvie, Enouf, Vincent, Levy, Yves, Wiedemann, Aurélie, Arowas, Laurence, Perlaza, Blanca, Perrin de Facci, Louise, Chaouche, Sophie, Sangari, Linda, Renaudat, Charlotte, Fernandes Pellerin, Sandrine, van Platen, Cassandre, Jolly, Nathalie, Kuhmel, Lucie, Garaud, Valentine, Rafanoson, Hantaniaina, Gardais, Soazic, de Parseval, Nathalie, Dugast, Claire, Jannet, Caroline, Ropars, Sandrine, Momboisse, Fanny, Porteret, Isabelle, Cailleau, Isabelle, Hoen, Bruno, Tondeur, Laura, Besombes, Camille, Fontanet, Arnaud, Dimitrov, Jordan, Simon-Lorière, Etienne, Bourhy, Hervé, Montagutelli, Xavier, Rey, Félix, Schwartz, Olivier, Mouquet, Hugo, Covid Cohort Study Group, French, Study Group, Corser, Immunologie humorale - Humoral Immunology, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Virologie Structurale - Structural Virology, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Virus et Immunité - Virus and immunity (CNRS-UMR3569), Vaccine Research Institute [Créteil, France] (VRI), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Lyssavirus, épidémiologie et neuropathologie - Lyssavirus Epidemiology and Neuropathology, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Génomique évolutive des virus à ARN - Evolutionary genomics of RNA viruses, Université Paris Cité (UPCité), École Doctorale Bio Sorbonne Paris Cité [Paris] (ED562 - BioSPC), Université Sorbonne Paris Cité (USPC)-Université Paris Cité (UPCité), Criblage chémogénomique et biologique (Plateforme) - Chemogenomic and Biological Screening Platform (PF-CCB), Laboratoire commun Pasteur-TheraVectys, Institut Pasteur [Paris] (IP)-TheraVectys-Université Paris Cité (UPCité), Génétique de la souris - Mouse Genetics, Génétique fonctionnelle des Maladies infectieuses - Functional Genetics of Infectious Diseases, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Centre d'investigation Clinique [CHU Bichat] - Épidémiologie clinique (CIC 1425), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Investigation Clinique et d’Accès aux Ressources Biologiques (Plate-forme) - Clinical Investigation and Access to BioResources (ICAReB), Génétique Moléculaire des Virus à ARN - Molecular Genetics of RNA Viruses (GMV-ARN (UMR_3569 / U-Pasteur_2)), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), FundingFunder(s): Institut PasteurFunder(s): French Government’s Investissements d’Avenir program Award Id(s): ANR-11-EQPX-0008Funder(s): Institut national de la santé et de la recherche médicaleFunder(s): REsearch & ACtion emergING infectious diseases (REACTing) consortiumFunder(s): Ministry of Health and Social AffairsFunder(s): Ministry of Higher Education and ResearchFunder(s): Agence Nationale de la Recherche Award Id(s): #20RR028-00Funder(s): European Commission Award Id(s): #101003589Funder(s): Fondation de France Award Id(s): #00106077Funder(s): Agence Nationale de Recherches sur le Sida et les Hépatites ViralesFunder(s): Programme hospitalier de recherche clinique Award Id(s): 20-0424, ANR-11-EQPX-0008,CACSICE,Centre d'analyse de systèmes complexes dans les environnements complexes(2011), ANR-21-CO14-0007,CoronaMito,Conséquences de l'infection par le SRAS-CoV-2 sur la fonction mitochondriale(2021), European Project: 101003589, H2020-SC1-PHE-CORONAVIRUS-2020,RECOVER(2020), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Virologie Structurale, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Virus et Immunité - Virus and immunity, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Vaccine Research Institute (VRI), Processus infectieux à Trypanosomatidés - Trypanosomatids Infectious Processes, Institut Pasteur [Paris]-Université Paris Cité (UPCité), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris], Interactions Virus-Insectes - Insect-Virus Interactions (IVI), and Institut Pasteur [Paris]-TheraVectys-Université Paris Cité (UPCité)
Subjects: [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, SARS-CoV-2, Immunoglobulin G, Spike Glycoprotein, Coronavirus, Immunology, Animals, COVID-19, Humans, Immunology and Allergy, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, Antibodies, Viral, Antibodies, Neutralizing, Immunoglobulin A
Abstract: International audience; Memory B-cell and antibody responses to the SARS-CoV-2 spike protein contribute to long-term immune protection against severe COVID-19, which can also be prevented by antibody-based interventions. Here, wide SARS-CoV-2 immunoprofiling in Wuhan COVID-19 convalescents combining serological, cellular, and monoclonal antibody explorations revealed humoral immunity coordination. Detailed characterization of a hundred SARS-CoV-2 spike memory B-cell monoclonal antibodies uncovered diversity in their repertoire and antiviral functions. The latter were influenced by the targeted spike region with strong Fc-dependent effectors to the S2 subunit and potent neutralizers to the receptor-binding domain. Amongst those, Cv2.1169 and Cv2.3194 antibodies cross-neutralized SARS-CoV-2 variants of concern, including Omicron BA.1 and BA.2. Cv2.1169, isolated from a mucosa-derived IgA memory B cell demonstrated potency boost as IgA dimers and therapeutic efficacy as IgG antibodies in animal models. Structural data provided mechanistic clues to Cv2.1169 potency and breadth. Thus, potent broadly neutralizing IgA antibodies elicited in mucosal tissues can stem SARS-CoV-2 infection, and Cv2.1169 and Cv2.3194 are prime candidates for COVID-19 prevention and treatment.
Published: 2022
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9. Sex Differences in the Evolution of Neutralizing Antibodies to Severe Acute Respiratory Syndrome Coronavirus 2

Author: Cyril Planchais, David Rey, Aurélie Velay, Ludivine Grzelak, Yoann Madec, Yves Hansmann, Isabelle Staropoli, Marie-Josée Wendling, Samira Fafi-Kremer, Arnaud Fontanet, Catherine Schmidt-Mutter, Timothée Bruel, Hugo Mouquet, Nathalie Reix, Ludovic Glady, Floriane Gallais, Olivier Schwartz, María González, Nicolas Meyer, Jérôme De Seze, Virus et Immunité - Virus and immunity, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Université Paris Cité (UPCité), Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Les Hôpitaux Universitaires de Strasbourg (HUS), Epidémiologie des Maladies Emergentes - Emerging Diseases Epidemiology, Pasteur-Cnam Risques infectieux et émergents (PACRI), Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), CIC Strasbourg (Centre d’Investigation Clinique Plurithématique (CIC - P) ), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Nouvel Hôpital Civil de Strasbourg-Hôpital de Hautepierre [Strasbourg], CHU Strasbourg, Groupe Méthodes en Recherche Clinique [Strasbourg] (GMRC), Nouvel Hôpital Civil [Strasbourg], CHU Strasbourg-CHU Strasbourg, Immunologie humorale - Humoral Immunology, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Vaccine Research Institute (VRI), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), S. F. K.’s laboratory is funded by Strasbourg University Hospitals (Hôpitaux Universitaires de Strasbourg, PRI 7782), Agence Nationale de la Recherche (ANR-18-CE17-0028), Laboratoire d’Excellence TRANSPLANTEX (ANR-11-LABX-0070_TRANSPLANTEX), and Institut National de la Santé et de la Recherche Médicale (UMR_S 1109). O. S.’s laboratory is funded by Institut Pasteur, Urgence COVID-19 Fundraising Campaign of Institut Pasteur, Agence Nationale de recherches sur le sida, Sidaction, the Vaccine Research Institute (ANR-10-LABX-77), Labex IBEID (ANR-10-LABX-62-IBEID), 'TIMTAMDEN' Agence Nationale de la Recherche ANR-14-CE14-0029, 'CHIKV-Viro-Immuno' ANR-14-CE14-0015-01, the Gilead HIV cure program, and ANR/Fondation Pour la Recherche Médicale Flash COVID. L. Gr., is supported by the French Ministry of Higher Education, Research and Innovation., ANR-18-CE17-0028,HuMABK,Les anticorps monoclonaux humains : une Nouvelle approche thérapeutique contre l'infection par le virus BK et les maladies associées(2018), ANR-11-LABX-0070,TRANSPLANTEX,Nouveaux loci d'histocompatibilité/biomarqueurs en transplantation humaine: de la découverte à l'app(2011), ANR-10-LABX-0077,VRI,Initiative for the creation of a Vaccine Research Institute(2010), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-14-CE14-0029,TIMTAMDEN,Rôle des récepteurs TIM et TAM dans l'infection des cellules cibles par le virus de la dengue(2014), ANR-14-CE14-0015,CHIKV-Viro-Immuno,Multiplication et Relation avec l'hôte du virus Chikungunya(2014), Virus et Immunité - Virus and immunity (CNRS-UMR3569), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Vaccine Research Institute [Créteil, France] (VRI), univOAK, Archive ouverte, APPEL À PROJETS GÉNÉRIQUE 2018 - Les anticorps monoclonaux humains : une Nouvelle approche thérapeutique contre l'infection par le virus BK et les maladies associées - - HuMABK2018 - ANR-18-CE17-0028 - AAPG2018 - VALID, Nouveaux loci d'histocompatibilité/biomarqueurs en transplantation humaine: de la découverte à l'app - - TRANSPLANTEX2011 - ANR-11-LABX-0070 - LABX - VALID, Laboratoires d'excellence - Initiative for the creation of a Vaccine Research Institute - - VRI2010 - ANR-10-LABX-0077 - LABX - VALID, Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - VALID, Appel à projets générique - Rôle des récepteurs TIM et TAM dans l'infection des cellules cibles par le virus de la dengue - - TIMTAMDEN2014 - ANR-14-CE14-0029 - Appel à projets générique - VALID, and Appel à projets générique - Multiplication et Relation avec l'hôte du virus Chikungunya - - CHIKV-Viro-Immuno2014 - ANR-14-CE14-0015 - Appel à projets générique - VALID
Subjects: 0301 basic medicine, sex-related differences, MESH: Spike Glycoprotein, Coronavirus, medicine.disease_cause, Immunoglobulin G, MESH: Antibodies, Neutralizing, law.invention, 03 medical and health sciences, 0302 clinical medicine, law, antibodies, MESH: COVID-19, Immunology and Allergy, Medicine, MESH: SARS-CoV-2, 030212 general & internal medicine, Polymerase chain reaction, Coronavirus, MESH: Immunoglobulin G, 2. Zero hunger, MESH: Humans, MESH: Middle Aged, biology, SARS-CoV-2, business.industry, COVID-19, MESH: Adult, MESH: Immunoglobulin M, MESH: Male, 3. Good health, 030104 developmental biology, Infectious Diseases, Real-time polymerase chain reaction, [INFO.INFO-TI] Computer Science [cs]/Image Processing [eess.IV], Immunoglobulin M, MESH: HEK293 Cells, [INFO.INFO-TI]Computer Science [cs]/Image Processing [eess.IV], Immunology, biology.protein, MESH: Health Personnel, Antibody, business, MESH: Female, Body mass index, MESH: Antibodies, Viral, MESH: Sex Characteristics, Sex characteristics
Abstract: We measured anti-spike (S), nucleoprotein (N), and neutralizing antibodies in sera from 308 healthcare workers with a positive reverse-transcription quantitative polymerase chain reaction result for severe acute respiratory syndrome coronavirus 2 and with mild disease, collected at 2 timepoints up to 6 months after symptom onset. At month 1, anti-S and -N antibody levels were higher in male participants aged >50 years and participants with a body mass index (BMI) >25 kg/m2. At months 3–6, anti-S and anti-N antibodies were detected in 99% and 59% of individuals, respectively. Anti-S antibodies and neutralizing antibodies declined faster in men than in women, independent of age and BMI, suggesting an association of sex with evolution of the humoral response.
Published: 2021
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10. A fourth dose of the mRNA-1273 SARS-CoV-2 vaccine improves serum neutralization against the Delta variant in kidney transplant recipients

Author: Olivier Schwartz, Delphine Planas, Ilies Benotmane, Samira Fafi-Kremer, Timothée Bruel, Sophie Caillard, CHU Strasbourg, Virus et Immunité - Virus and immunity (CNRS-UMR3569), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Vaccine Research Institute [Créteil, France] (VRI), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Virus et Immunité - Virus and immunity, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), and Vaccine Research Institute (VRI)
Subjects: Delta, Delta variant, COVID-19 Vaccines, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Alpha (ethology), kidney transplantation, neutralizing antibodies, Antibodies, Viral, fourth dose, Immune system, Neutralization test, Humans, Medicine, Neutralizing antibody, Messenger RNA, biology, business.industry, SARS-CoV-2, COVID-19, Antibodies, Neutralizing, Transplant Recipients, Titer, mRNA vaccine, Nephrology, Immunology, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, biology.protein, business, 2019-nCoV Vaccine mRNA-1273
Abstract: In immunocompetent subjects, the effectiveness of SARS-CoV-2 vaccines against the delta variant appears three- to five-fold lower than that observed against the alpha variant. Additionally, three doses of SARS-CoV-2 mRNA-based vaccines might be unable to elicit a sufficient immune response against any variant in immunocompromised kidney transplant recipients. This study describes the kinetics of the neutralizing antibody (NAbs) response against the delta strain before and after a fourth dose of a mRNA vaccine in 67 kidney transplant recipients who had experienced a weak antibody response after three doses. While only 16% of patients harbored NAbs against the delta strain prior to the fourth injection – this percentage raised to 66% afterwards. We also found that, after the fourth dose, the NAbs titer increased significantly (p=0.0001) from
Published: 2022
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11. Towards SARS-CoV-2 serotypes?

Author: OLIVIER SCHWARTZ, Mi-Hua Tao, Génomique évolutive des virus à ARN - Evolutionary genomics of RNA viruses, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Virus et Immunité - Virus and immunity (CNRS-UMR3569), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Vaccine Research Institute [Créteil, France] (VRI), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), The authors thank D. Planas, T. Bruel, H. Mouquet and A. Fontanet for critical reading and contributing and originating laboratories for sequences., Institut Pasteur [Paris]-Université Paris Cité (UPCité), Virus et Immunité - Virus and immunity, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), and Vaccine Research Institute (VRI)
Subjects: General Immunology and Microbiology, SARS-CoV-2, viruses, fungi, COVID-19, biochemical phenomena, metabolism, and nutrition, Serogroup, Microbiology, body regions, Infectious Diseases, Spike Glycoprotein, Coronavirus, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Humans, skin and connective tissue diseases
Abstract: International audience; The magnitude of immune evasion of Omicron raises the question whether it should be considered as a distinct SARS-CoV-2 serotype. Here, we discuss lines of evidence in support or against the concept of SARS-CoV-2 serotypes, and the implications of this classification.
Published: 2022
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12. Serum neutralization of SARS-CoV-2 Omicron sublineages BA.1 and BA.2 in patients receiving monoclonal antibodies

Author: Timothée Bruel, Jérôme Hadjadj, Piet Maes, Delphine Planas, Aymeric Seve, Isabelle Staropoli, Florence Guivel-Benhassine, Françoise Porrot, William-Henry Bolland, Yann Nguyen, Marion Casadevall, Caroline Charre, Hélène Péré, David Veyer, Matthieu Prot, Artem Baidaliuk, Lize Cuypers, Cyril Planchais, Hugo Mouquet, Guy Baele, Luc Mouthon, Laurent Hocqueloux, Etienne Simon-Loriere, Emmanuel André, Benjamin Terrier, Thierry Prazuck, Olivier Schwartz, Virus et Immunité - Virus and immunity (CNRS-UMR3569), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Vaccine Research Institute [Créteil, France] (VRI), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre Hospitalier Régional d'Orléans (CHRO), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), University Hospitals Leuven [Leuven], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Génomique évolutive des virus à ARN - Evolutionary genomics of RNA viruses, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Immunologie humorale - Humoral Immunology, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Génomique fonctionnelle des tumeurs solides = Functional Genomics of Solid Tumors [CRC] (FunGeST), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Université Paris Cité (UPCité), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), École Doctorale Bio Sorbonne Paris Cité [Paris] (ED562 - BioSPC), Université Sorbonne Paris Cité (USPC)-Université Paris Cité (UPCité), Work in the O.S. lab is funded by Institut Pasteur, Urgence COVID-19 Fundraising Campaign of Institut Pasteur, Fondation pour la Recherche Médicale (FRM), ANRS, the Vaccine Research Institute (ANR-10-LABX-77), Labex IBEID (ANR-10-LABX-62-IBEID), ANR/FRM Flash Covid PROTEO-SARS-CoV-2, ANR Coronamito and IDISCOVR. Work in the UPBI facility is funded by grant ANR-10-INSB-04-01 and the Région Ȋle-de-France program DIM1Health. D.P. is supported by the Vaccine Research Institute. G.B. acknowledges support from the Internal Funds KU Leuven under grant agreement C14/18/094 and the Research Foundation–Flanders (Fonds voor Wetenschappelijk Onderzoek–Vlaanderen, G0E1420N and G098321N). P.M. acknowledges support from a COVID-19 research grant of ‘Fonds Wetenschappelijk Onderzoek’/Research Foundation Flanders (grant G0H4420N). P.M. acknowledges support of a COVID-19 research grant from ‘Fonds Wetenschappelijk Onderzoek’/Research Foundation Flanders (grant G0H4420N) and ‘Internal Funds KU Leuven’ (grant 3M170314). E.S.L. acknowledges funding from the INCEPTION program (Investissements d’Avenir grant ANR-16-CONV-0005)., We thank the European Health Emergency Preparedness and Response Authority (HERA) for supporting the work being done at Institut Pasteur and UK Leuven. We thank J. Buchrieser, J. Puech and F. Gambaro for their help with the sequencing data analysis. We thank the patients who participated to this study. We thank Y. Yazdanpanah, members of the Virus and Immunity Unit and other teams for discussions and help, N. Aulner and the UtechS Photonic BioImaging (UPBI) core facility (Institut Pasteur), a member of the France BioImaging network, for image acquisition and analysis. The Opera system was co-funded by Institut Pasteur and the Région Ȋle-de-France (DIM1Health). We thank the KU Leuven University authorities and J. Arnout, B. Lambrecht, C. Van Geet and L. Sels for their support. We thank F. Peira, V. Legros and L. Courtellemont for their help with the cohorts. UZ Leuven, as national reference center for respiratory pathogens, is supported by Sciensano, which is gratefully acknowledged., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-20-COVI-0059,PROTEO-SARS-CoV-2,Protéomique du SARS-CoV-2(2020), ANR-10-LABX-0077,VRI,Initiative for the creation of a Vaccine Research Institute(2010), ANR-21-CO14-0007,CoronaMito,Conséquences de l'infection par le SRAS-CoV-2 sur la fonction mitochondriale(2021), ANR-10-INBS-0004,France-BioImaging,Développment d'une infrastructure française distribuée coordonnée(2010), ANR-16-CONV-0005,INCEPTION,Institut Convergences pour l'étude de l'Emergence des Pathologies au Travers des Individus et des populatiONs(2016), Virus et Immunité - Virus and immunity, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Vaccine Research Institute (VRI), Institut Pasteur [Paris]-Université Paris Cité (UPCité), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), École pratique des hautes études (EPHE), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)-École pratique des hautes études (EPHE)
Subjects: Membrane Glycoproteins, SARS-CoV-2, Antibodies, Monoclonal, General Medicine, Antibodies, Monoclonal, Humanized, Antibodies, Viral, Antibodies, Neutralizing, General Biochemistry, Genetics and Molecular Biology, COVID-19 Drug Treatment, Viral Envelope Proteins, Neutralization Tests, Spike Glycoprotein, Coronavirus, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Humans
Abstract: International audience; The severe acute respiratory syndrome coronavirus 2 Omicron BA.1 sublineage has been supplanted in many countries by the BA.2 sublineage. BA.2 differs from BA.1 by about 21 mutations in its spike. In this study, we first compared the sensitivity of BA.1 and BA.2 to neutralization by nine therapeutic monoclonal antibodies (mAbs). In contrast to BA.1, BA.2 was sensitive to cilgavimab, partly inhibited by imdevimab and resistant to adintrevimab and sotrovimab. We then analyzed sera from 29 immunocompromised individuals up to 1 month after administration of Ronapreve (casirivimab and imdevimab) and/or Evusheld (cilgavimab and tixagevimab) antibody cocktails. All treated individuals displayed elevated antibody levels in their sera, which efficiently neutralized the Delta variant. Sera from Ronapreve recipients did not neutralize BA.1 and weakly inhibited BA.2. Neutralization of BA.1 and BA.2 was detected in 19 and 29 out of 29 Evusheld recipients, respectively. As compared to the Delta variant, neutralizing titers were more markedly decreased against BA.1 (344-fold) than BA.2 (nine-fold). We further report four breakthrough Omicron infections among the 29 individuals, indicating that antibody treatment did not fully prevent infection. Collectively, BA.1 and BA.2 exhibit noticeable differences in their sensitivity to therapeutic mAbs. Anti-Omicron neutralizing activity of Ronapreve and, to a lesser extent, that of Evusheld is reduced in patients' sera.
Published: 2022
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13. Case Report: Evolution of Humoral and Cellular Immunity in Two COVID-19 Breakthrough Infections After BNT162b2 Vaccine

Author: Floriane Gallais, Pierre Gantner, Delphine Planas, Morgane Solis, Timothée Bruel, Florian Pierre, Eric Soulier, Paola Rossolillo, Slim Fourati, Jean Sibilia, Olivier Schwartz, Samira Fafi-Kremer, Laboratoire de Virologie [Strasbourg], Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Virus et Immunité - Virus and immunity, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPC), Vaccine Research Institute (VRI), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Les Hôpitaux Universitaires de Strasbourg (HUS), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre for Integrative Biology - CBI (Inserm U964 - CNRS UMR7104 - IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Strasbourg, This work was supported by the Strasbourg University Hospital (SeroCoV-HUS, PRI 7782), ANR-18-CE17-0028, ANR-11-LABX-0070_TRANSPLANTEX, Strasbourg University and the Institut National de la Santé et de la Recherche Médicale (UMR_S 1109). Work in OS lab is funded by the Institut Pasteur, Urgence COVID-19 Fundraising Campaign of Institut Pasteur, Fondation pour la Recherche Médicale (FRM), ANRS, the Vaccine Research Institute (ANR-10-LABX-77), Labex IBEID (ANR-10-LABX-62-IBEID), ANR/FRM Flash Covid PROTEO-SARS-CoV-2 and IDISCOVR. DP is supported by the Vaccine Research Institute., We are grateful to the participants of the study. We thank Dr. Negar Sedghi and Dr. Dominique Desprez for reporting us the breakthrough cases., ANR-11-LABX-0070,TRANSPLANTEX,Nouveaux loci d'histocompatibilité/biomarqueurs en transplantation humaine: de la découverte à l'app(2011), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-20-COVI-0059,PROTEO-SARS-CoV-2,Protéomique du SARS-CoV-2(2020), ANR-10-LABX-0077,VRI,Initiative for the creation of a Vaccine Research Institute(2010), Virus et Immunité - Virus and immunity (CNRS-UMR3569), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Vaccine Research Institute [Créteil, France] (VRI), and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)
Subjects: MESH: Humans, MESH: Middle Aged, SARS-CoV-2, Immunology, breakthrough infection, MESH: CD4-Positive T-Lymphocytes, MESH: Adult, MESH: Vaccination, MESH: CD8-Positive T-Lymphocytes, MESH: Antibodies, Neutralizing, MESH: COVID-19 Vaccines, vaccine, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Immunology and Allergy, MESH: COVID-19, MESH: SARS-CoV-2, MESH: Immune Evasion, MESH: BNT162 Vaccine, variant of concern, MESH: Female, MESH: Antibodies, Viral, immune evasion
Abstract: BackgroundSARS-CoV-2 breakthrough infections after complete vaccination are increasing whereas their determinants remain uncharacterized.MethodsWe analyzed two cases of post-vaccination SARS-CoV-2 infections by α and β variants, respectively. For each participant both humoral (binding and neutralizing antibodies) and cellular (activation markers and cytokine expression) immune responses were characterized longitudinally.ResultsThe first participant (P1) was infected by an α variant and displayed an extended and short period of viral excretion and symptom. Analysis of cellular and humoral response 72 h post-symptom onset revealed that P1 failed at developing neutralizing antibodies and a potent CD4 memory response (lack of SARS-CoV-2 specific CD4+IL-2+ cells) and CD8 effector response (CD8+IFNγ+ cells). The second participant (P2) developed post-vaccination SARS-CoV-2 infection by a β variant, associated with a short period of viral excretion and symptoms. Despite displaying initially high levels and polyfunctional T cell responses, P2 lacked initial β-directed neutralizing antibodies. Both participants developed and/or increased their neutralization activity and cellular responses against all variants, namely, β and δ variants that lasts up to 3 months after breakthrough infection.ConclusionsAn analysis of cellular and humoral response suggests two possible mechanisms of breakthrough infection: a poor immune response to vaccine and viral evasion to neutralizing antibodies.
Published: 2022
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14. Severe relapse of SARS‐CoV‐2 infection in a kidney transplant recipient with negative nasopharyngeal SARS‐CoV‐2 RT‐PCR after rituximab

Author: Antoine Morel, Sandrine Imbeaud, Anne Scemla, Hélène Péré, Jacques Fourgeaud, Lucile Amrouche, Nicolas Robillard, Delphine Planas, Julien Puech, Sylvie Simon, Fanny Lanternier, Laurent Bélec, Julien Zuber, Olivier Schwartz, Dany Anglicheau, Nathalie Chavarot, David Veyer, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPC), Génomique fonctionnelle des tumeurs solides = Functional Genomics of Solid Tumors [CRC] (FunGeST), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPC)-École pratique des hautes études (EPHE), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Laboratoire de Microbiologie Clinique [AP-HP Hôpital Necker-Enfants Malades], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Virus et Immunité - Virus and immunity, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPC), Vaccine Research Institute (VRI), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC), Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPC), The authors would like to thank AcaciaTools for their proofreading services, École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)-École Pratique des Hautes Études (EPHE), Virus et Immunité - Virus and immunity (CNRS-UMR3569), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Université Paris-Saclay, Service Néphrologie et transplantation rénale Adultes [CHU Necker], Université Sorbonne Paris Cité (USPC), Laboratoire de Virologie [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Université Paris Descartes - Paris 5 (UPD5), Vaccine Research Institute [Créteil, France] (VRI), Université Paris Cité (UPCité), Université Paris Diderot - Paris 7 (UPD7), Laboratoire de Virologie [Hôpital Européen Georges Pompidou - APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)-École pratique des hautes études (EPHE), and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)
Subjects: Transplantation, MESH: Humans, infection and infectious agents-viral, translational research/science, [SDV]Life Sciences [q-bio], infectious disease, MESH: COVID-19 Testing, kidney transplantation/nephrology, clinical research/practice, MESH: Kidney Transplantation, MESH: Recurrence, lung disease: infectious, MESH: Reverse Transcriptase Polymerase Chain Reaction, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Immunology and Allergy, MESH: COVID-19, Pharmacology (medical), MESH: SARS-CoV-2, MESH: Rituximab
Abstract: International audience; Immunocompromised patients may experience prolonged viral shedding after their initial SARS-CoV-2 infection, however, symptomatic relapses after remission currently remain rare. We herein describe a severe COVID-19 relapse case of a kidney transplant recipient (KTR) following rituximab therapy, 3 months after a moderate COVID-19 infection, despite viral clearance after recovery of the first episode. During the clinical relapse, the diagnosis was established on a broncho-alveolar lavage specimen (BAL) by RT-PCR. The infectivity of the BAL sample was confirmed on a cell culture assay. Whole genome sequencing confirmed the presence of an identical stain (Clade 20A). However, it had an acquired G142D mutation and a larger deletion of 3-amino-acids at position 143-145. These mutations located within the N-terminal domain are suggested to play a role in viral entry. The diagnosis of a COVID-19 relapse should be considered in the setting of unexplained persistent fever and/or respiratory symptoms in KTRs (especially for those after rituximab therapy), even in patients with previous negative naso-pharyngeal SARS-CoV-2 PCR.
Published: 2022
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15. Anti-CD38 therapy impairs SARS-CoV-2 vaccine response against alpha and delta variants in patients with multiple myeloma

Author: Soledad Henriquez, Jérémie Zerbit, Timothée Bruel, Amani Ouedrani, Delphine Planas, Paul Deschamps, Isabelle Staropoli, Jérôme Hadjadj, Bruno Varet, Natalia Ermak, Didier Bouscary, Lise Willems, Guillemette Fouquet, Justine Decroocq, Patricia Franchi, Benedicte Deau-Fischer, Benjamin Terrier, Jérôme Tamburini, Lucienne Chatenoud, Olivier Schwartz, Marguerite Vignon, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Virus et Immunité - Virus and immunity, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Vaccine Research Institute (VRI), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Necker - Enfants Malades [AP-HP], Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPC), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC), Université de Genève (UNIGE), Université Paris Descartes - Paris 5 (UPD5), This study was supported by Fonds IMMUNOV for Innovation in Immunopathology, by the Institut Pasteur (for work in the OS laboratory), the Urgence COVID-19 Fundraising Campaign of Institut Pasteur, Fondation pour la Recherche Médicale, and ANRS, and by grants from the Vaccine Research Institute (ANR-10-LABX-77), Labex IBEID (ANR-10-LABX-62-IBEID), ANR/FRM Flash Covid PROTEO-SARS-CoV-2, and IDISCOVR. D.P. is supported by the Vaccine Research Institute., ANR-10-LABX-0077,VRI,Initiative for the creation of a Vaccine Research Institute(2010), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-20-COVI-0059,PROTEO-SARS-CoV-2,Protéomique du SARS-CoV-2(2020), Virus et Immunité - Virus and immunity (CNRS-UMR3569), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Vaccine Research Institute [Créteil, France] (VRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), and Université de Genève = University of Geneva (UNIGE)
Subjects: Immunology, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Cell Biology, Hematology, Biochemistry, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2022
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16. High negative predictive value of RT-PCR in patients with high likelihood of SARS-CoV-2 infection

Author: S. Galmiche, S. Fernandes-Pellerin, M.N. Ungeheuer, O. Schwartz, M. Attia, B. Hoen, J.-P. Lanoix, T. Guimard, J.-M. Chapplain, F. Goehringer, J.-F. Faucher, P. Chavanet, F. Cazenave-Roblot, T. Prazuck, Epidémiologie des Maladies Emergentes - Emerging Diseases Epidemiology, Université Paris Cité (UPCité)-Pasteur-Cnam Risques infectieux et émergents (PACRI), Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Paris Cité (UPCité)-Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), Centre de Recherche Translationnelle - Center for Translational Science (CRT), Institut Pasteur [Paris]-Université Paris Cité (UPCité), Investigation Clinique et d’Accès aux Ressources Biologiques (Plate-forme) - Clinical Investigation and Access to BioResources (ICAReB), Virus et Immunité - Virus and immunity, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Vaccine Research Institute (VRI), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Génétique Moléculaire des Virus à ARN - Molecular Genetics of RNA Viruses (GMV-ARN (UMR_3569 / U-Pasteur_2)), Centre National de Référence des virus des infections respiratoires (dont la grippe) - National Reference Center Virus Influenzae [Paris] (CNR), The study was funded by Institut Pasteur, Fondation BTP Plus, and Fondation Total. Several laboratories participating in the study receive funding from the Labex IBEID (ANR-10-LABX-62-IBEID), REACTing and the INCEPTION project (PIA/ANR-16-CONV-0005) for studies focusing on emerging viruses. OS lab is funded by Institut Pasteur, ANRS, Sidaction, the Vaccine Research Institute (ANR- 10-LABX-77), 'TIMTAMDEN' ANR-14-CE14-0029, 'CHIKV-Viro- Immuno' ANR-14-CE14-0015-01 and the Gilead HIV cure program., CORSER-2A study group: J-P Lanoix, T Guimard, J-M Chapplain, F Goehringer, J-F Faucher , P Chavanet , F Cazenave-Roblot , T Prazuck, We would like to thank collaborators at the Institut Pasteur, Linda Sangari, Sophie Chaouche, Dr Charlotte Renaudat at the ICAReB platform, Thomas Obadia at the Bioinformatics and Biostatistics Hub, Cassandre von Platen and Tan-Phuc Buivan at the Center for Translational Sciences., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-08-BLAN-0046,REACTING,Reactivity of inorganic radicals in aqueous solution(2008), ANR-16-CONV-0005,INCEPTION,Institut Convergences pour l'étude de l'Emergence des Pathologies au Travers des Individus et des populatiONs(2016), ANR-10-LABX-0077,VRI,Initiative for the creation of a Vaccine Research Institute(2010), ANR-14-CE14-0029,TIMTAMDEN,Rôle des récepteurs TIM et TAM dans l'infection des cellules cibles par le virus de la dengue(2014), ANR-14-CE14-0015,CHIKV-Viro-Immuno,Multiplication et Relation avec l'hôte du virus Chikungunya(2014), Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Paris Cité (UPCité)-Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), DESSAIVRE, Louise, Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - VALID, Blanc - Reactivity of inorganic radicals in aqueous solution - - REACTING2008 - ANR-08-BLAN-0046 - BLANC - VALID, Institut Convergences pour l'étude de l'Emergence des Pathologies au Travers des Individus et des populatiONs - - INCEPTION2016 - ANR-16-CONV-0005 - CONV - VALID, Laboratoires d'excellence - Initiative for the creation of a Vaccine Research Institute - - VRI2010 - ANR-10-LABX-0077 - LABX - VALID, Appel à projets générique - Rôle des récepteurs TIM et TAM dans l'infection des cellules cibles par le virus de la dengue - - TIMTAMDEN2014 - ANR-14-CE14-0029 - Appel à projets générique - VALID, Appel à projets générique - Multiplication et Relation avec l'hôte du virus Chikungunya - - CHIKV-Viro-Immuno2014 - ANR-14-CE14-0015 - Appel à projets générique - VALID, Virus et Immunité - Virus and immunity (CNRS-UMR3569), Vaccine Research Institute [Créteil, France] (VRI), and Centre National de Référence des virus des infections respiratoires (dont la grippe) - National Reference Center Virus Influenzae [Paris] (CNR - laboratoire coordonnateur)
Subjects: 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), [SDV]Life Sciences [q-bio], RT-PCR, Sensitivity and Specificity, Article, Predictive Value of Tests, MESH: Reverse Transcriptase Polymerase Chain Reaction, Medicine, Humans, MESH: COVID-19, High likelihood, In patient, MESH: SARS-CoV-2, ComputingMilieux_MISCELLANEOUS, MESH: Humans, business.industry, Reverse Transcriptase Polymerase Chain Reaction, SARS-CoV-2, COVID-19, Virology, Predictive value, MESH: Predictive Value of Tests, MESH: Sensitivity and Specificity, [SDV] Life Sciences [q-bio], Infectious Diseases, Real-time polymerase chain reaction, business
Abstract: International audience
Published: 2022
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17. Robust and Functional Immune Memory Up to 9 Months After SARS-CoV-2 Infection: A Southeast Asian Longitudinal Cohort

Author: Hoa Thi My Vo, Alvino Maestri, Heidi Auerswald, Sopheak Sorn, Sokchea Lay, Heng Seng, Sotheary Sann, Nisa Ya, Polidy Pean, Philippe Dussart, Olivier Schwartz, Sovann Ly, Timothée Bruel, Sowath Ly, Veasna Duong, Erik A. Karlsson, Tineke Cantaert, Institut Pasteur du Cambodge, Réseau International des Instituts Pasteur (RIIP), Communicable Disease Department [Phnom Penh] (CDC MOH), Ministry of Health [Mozambique], Virus et Immunité - Virus and immunity (CNRS-UMR3569), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Vaccine Research Institute [Créteil, France] (VRI), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), The Howard Hughes Medical Institute (HHMI)–Wellcome Trust (208710/Z/17/Z to TC), « URGENCE COVID-19 » fundraising campaign of Institut Pasteur (TC, HA, and PD). HA is supported by the German Centre for International Migration and Development (CIM)., Virus et Immunité - Virus and immunity, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), and Vaccine Research Institute (VRI)
Subjects: CD4-Positive T-Lymphocytes, Immunology, MESH: Spike Glycoprotein, Coronavirus, CD8-Positive T-Lymphocytes, B cell immunity, Antibodies, Viral, MESH: Phosphoproteins, long term immune response, MESH: Antibodies, Neutralizing, MESH: Immunity, Cellular, Immunology and Allergy, Coronavirus Nucleocapsid Proteins, Humans, MESH: COVID-19, MESH: Coronavirus Nucleocapsid Proteins, MESH: SARS-CoV-2, MESH: Immunity, Humoral, B-Lymphocytes, Immunity, Cellular, MESH: Humans, T cell immunity, SARS-CoV-2, MESH: Cambodia, COVID-19, MESH: CD4-Positive T-Lymphocytes, RC581-607, Phosphoproteins, Antibodies, Neutralizing, MESH: CD8-Positive T-Lymphocytes, Immunity, Humoral, antibody effector function, Spike Glycoprotein, Coronavirus, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, MESH: Immunologic Memory, Immunologic diseases. Allergy, Cambodia, Immunologic Memory, MESH: Antibodies, Viral
Abstract: The duration of humoral and cellular immune memory following SARS-CoV-2 infection in populations in least developed countries remains understudied but is key to overcome the current SARS-CoV-2 pandemic. Sixty-four Cambodian individuals with laboratory-confirmed infection with asymptomatic or mild/moderate clinical presentation were evaluated for Spike (S)-binding and neutralizing antibodies and antibody effector functions during acute phase of infection and at 6-9 months follow-up. Antigen-specific B cells, CD4+ and CD8+ T cells were characterized, and T cells were interrogated for functionality at late convalescence. Anti-S antibody titers decreased over time, but effector functions mediated by S-specific antibodies remained stable. S- and nucleocapsid (N)-specific B cells could be detected in late convalescence in the activated memory B cell compartment and are mostly IgG+. CD4+ and CD8+ T cell immune memory was maintained to S and membrane (M) protein. Asymptomatic infection resulted in decreased antibody-dependent cellular cytotoxicity (ADCC) and frequency of SARS-CoV-2-specific CD4+ T cells at late convalescence. Whereas anti-S antibodies correlated with S-specific B cells, there was no correlation between T cell response and humoral immune memory. Hence, all aspects of a protective immune response are maintained up to nine months after SARS-CoV-2 infection and in the absence of re-infection.
Published: 2022
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18. Neutralising antibody responses to SARS-CoV-2 omicron among elderly nursing home residents following a booster dose of BNT162b2 vaccine: A community-based, prospective, longitudinal cohort study

Author: Timothée Bruel, Laurie Pinaud, Laura Tondeur, Delphine Planas, Isabelle Staropoli, Françoise Porrot, Florence Guivel-Benhassine, Mikaël Attia, Stéphane Pelleau, Tom Woudenberg, Cécile Duru, Aymar Davy Koffi, Sandrine Castelain, Sandrine Fernandes-Pellerin, Nathalie Jolly, Louise Perrin De Facci, Emmanuel Roux, Marie-Noëlle Ungeheuer, Sylvie Van Der Werf, Michael White, Olivier Schwartz, Arnaud Fontanet, Virus et Immunité - Virus and immunity (CNRS-UMR3569), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Vaccine Research Institute [Créteil, France] (VRI), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Epidémiologie des Maladies Emergentes - Emerging Diseases Epidemiology, Université Paris Cité (UPCité)-Pasteur-Cnam Risques infectieux et émergents (PACRI), Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Paris Cité (UPCité)-Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), Génétique Moléculaire des Virus à ARN - Molecular Genetics of RNA Viruses (GMV-ARN (UMR_3569 / U-Pasteur_2)), Epidémiologie et Analyse des Maladies Infectieuses - Infectious Disease Epidemiology and Analytics, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Hôpital de Crépy-en-Valois, Agents infectieux, résistance et chimiothérapie - UR UPJV 4294 (AGIR ), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Centre de Recherche Translationnelle - Center for Translational Science (CRT), Investigation Clinique et d’Accès aux Ressources Biologiques (Plate-forme) - Clinical Investigation and Access to BioResources (ICAReB), Pasteur-Cnam Risques infectieux et émergents (PACRI), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Paris Cité (UPCité), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), Work in OS lab is funded by Institut Pasteur, Urgence COVID-19 Fundraising Campaign of Institut Pasteur, Fondation pour la Recherche Médicale (FRM), the European Health Emergency Preparedness and Response Authority (HERA), ANRS-MIE, the Vaccine Research Institute (ANR-10-LABX-77), Labex IBEID (ANR-10-LABX-62-IBEID), ANR/FRM Flash Covid PROTEO-SARS-CoV-2, ANR Coronamito, and IDISCOVR, 'TIMTAMDEN' ANR-14-CE14-0029, 'CHIKV-Viro- Immuno' ANR-14-CE14-0015-01 and the Gilead HIV cure program. AF lab is funded by the INCEPTION project (PIA/ANR-16-CONV-0005) and the Labex IBEID (ANR-10-LABX-62-IBEID). The COVID-Oise cohort is funded by 'Alliance Tous Unis contre le virus' Institut Pasteur, AP-HP and Fondation de France., ANR-10-LABX-0077,VRI,Initiative for the creation of a Vaccine Research Institute(2010), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-20-COVI-0059,PROTEO-SARS-CoV-2,Protéomique du SARS-CoV-2(2020), ANR-14-CE14-0029,TIMTAMDEN,Rôle des récepteurs TIM et TAM dans l'infection des cellules cibles par le virus de la dengue(2014), ANR-14-CE14-0015,CHIKV-Viro-Immuno,Multiplication et Relation avec l'hôte du virus Chikungunya(2014), ANR-16-CONV-0005,INCEPTION,Institut Convergences pour l'étude de l'Emergence des Pathologies au Travers des Individus et des populatiONs(2016), Virus et Immunité - Virus and immunity, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Vaccine Research Institute (VRI), Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Paris Cité (UPCité)-Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM), and Institut Pasteur [Paris]-Université Paris Cité (UPCité)
Subjects: [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, SARS-CoV-2, Omicron, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.MHEP.GEG]Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, Elderly individuals, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, General Medicine, [SDV.IMM.VAC]Life Sciences [q-bio]/Immunology/Vaccinology, Vaccine, Antibodies
Abstract: International audience; BACKGROUND: The protective immunity against omicron following a BNT162b2 Pfizer booster dose among elderly individuals (ie, those aged >65 years) is not well characterised.METHODS: In a community-based, prospective, longitudinal cohort study taking place in France in which 75 residents from three nursing homes were enrolled, we selected 38 residents who had received a two-dose regimen of mRNA vaccine and a booster dose of Pfizer BNT162b2 vaccine. We excluded individuals that did not receive three vaccine doses or did not have available sera samples. We measured anti-S IgG antibodies and neutralisation capacity in sera taken 56 (28-68) and 55 (48-64) days (median (range)) after the 2(nd) and 3(rd) vaccine doses, respectively. Antibodies targeting the SARS-CoV-2 Spike protein were measured with the S-Flow assay as binding antibody units per milliliter (BAU/mL). Neutralising activities in sera were measured as effective dilution 50% (ED50) with the S-Fuse assay using authentic isolates of delta and omicron BA.1.FINDINGS: Among the 38 elderly individuals recruited to the cohort study between November 23(rd), 2020 and April 29(th), 2021, with median age of 88 (range 72-101) years, 30 (78.95%) had been previously infected with SARS-CoV-2. After three vaccine doses, serum neutralising activity was lower against omicron BA.1 (median ED50 of 774.5, range 15.0-34660.0) than the delta variant (median ED50 of 4972.0, range 213.7-66340.0), and higher among previously infected (ie, convalescent; median ED50 against omicron: 1088.0, range 32.6-34660.0) compared with infection-naive residents (median ED50 against omicron: 188.4, range 15.0-8918.0). During the French omicron wave in December 2021-January 2022, 75% (6/8) of naive residents were infected, compared to 25% (7/30) of convalescent residents (P=0.0114). Anti-Spike antibody levels and neutralising activity against omicron BA.1 after a third BNT162b2 booster dose were lower in those with breakthrough BA.1 infection (n=13) compared with those without (n=25), with a median of 1429.9 (range 670.9-3818.3) BAU/mL vs 2528.3 (range 695.4-8832.0) BAU/mL (P=0.029) and a median ED50 of 281.1 (range 15.0-2136.0) vs 1376.0 (range 32.6-34660.0) (P=0.0013), respectively.INTERPRETATION: This study shows that elderly individuals who received three vaccine doses elicit neutralising antibodies against the omicron BA.1 variant of SARS-CoV-2. Elderly individuals who had also been previously infected showed higher neutralising activity compared with naive individuals. Yet, breakthrough infections with omicron occurred. Individuals with breakthrough infections had significantly lower neutralising titers compared to individuals without breakthrough infection. Thus, a fourth dose of vaccine may be useful in the elderly population to increase the level of neutralising antibodies and compensate for waning immunity.
Published: 2022
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19. C910 chemical compound inhibits the traffiking of several bacterial AB toxins with cross-protection against influenza virus

Author: Yu Wu, Nassim Mahtal, Eléa Paillares, Léa Swistak, Sara Sagadiev, Mridu Acharya, Caroline Demeret, Sylvie Van Der Werf, Florence Guivel-Benhassine, Olivier Schwartz, Serena Petracchini, Amel Mettouchi, Lucie Caramelle, Pierre Couvineau, Robert Thai, Peggy Barbe, Mathilde Keck, Priscille Brodin, Arnaud Machelart, Valentin Sencio, François Trottein, Martin Sachse, Gaëtan Chicanne, Bernard Payrastre, Florian Ville, Victor Kreis, Michel-Robert Popoff, Ludger Johannes, Jean-Christophe Cintrat, Julien Barbier, Daniel Gillet, Emmanuel Lemichez, TROTTEIN, François, Caractérisation d'un composé antitoxines bactériennes à large spectre - - ToxProtect_Larg_Spectr2019 - ANR-19-ASTR-0001 - ASTRID - VALID, Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - VALID, Research Laboratory on Drugs and Therapeutic Innovation - - LERMIT2010 - ANR-10-LABX-0033 - LABX - VALID, Toxines bactériennes - Bacterial Toxins, Université Paris Cité (UPCité)-Microbiologie Intégrative et Moléculaire (UMR6047), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'Ingénierie Moléculaire pour la Santé (ex SIMOPRO) (SIMoS), Médicaments et Technologies pour la Santé (MTS), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Service de Chimie Bio-Organique et de Marquage (SCBM), Seattle Children's Research Institute [Seattle, WA, USA], Génétique Moléculaire des Virus à ARN - Molecular Genetics of RNA Viruses (GMV-ARN (UMR_3569 / U-Pasteur_2)), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Virus et Immunité - Virus and immunity, Université Paris-Saclay, Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), CHU Lille, Plateforme BioImagerie Ultrastructurale – Ultrastructural BioImaging Platform (UTechS UBI), Institut Pasteur [Paris] (IP), Institut des Maladies Métaboliques et Casdiovasculaires (UPS/Inserm U1297 - I2MC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Chimie biologique des membranes et ciblage thérapeutique (CBMCT - UMR 3666 / U1143), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), This work was funded by the joint ministerial program of Research and Development against Chemical, Biological, Radiological, Nuclear and Explosive risks ( CBRNE ), grants from the Agence Nationale de la Recherche ( ANR-19-ASTR-0001 ), Labex IBEID ( ANR-10-LABX-62-IBEID ), and the French Alternative Energies and Atomic Energy Commission ( CEA ). N.M., E.P., L.C., and F.V. were supported by DGA-MRIS/AID scholarships with CEA or Pasteur. SIMoS and SCBM are members of the Laboratory of Excellence LERMIT and were supported by a grant from the Agence Nationale de la Recherche ( ANR-10-LABX-33 )., ANR-19-ASTR-0001,ToxProtect_Larg_Spectr,Caractérisation d'un composé antitoxines bactériennes à large spectre(2019), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-10-LABX-0033,LERMIT,Research Laboratory on Drugs and Therapeutic Innovation(2010), Virus et Immunité - Virus and immunity (CNRS-UMR3569), and Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: [SDV] Life Sciences [q-bio], Biological sciences, Multidisciplinary, [SDV]Life Sciences [q-bio], Microbiology
Abstract: International audience; The development of anti-infectives against a large range of AB-like toxin-producing bacteria includes the identification of compounds disrupting toxin transport through both the endolysosomal and retrograde pathways. Here, we performed a high-throughput screening of compounds blocking Rac1 proteasomal degradation triggered by the Cytotoxic Necrotizing Factor-1 (CNF1) toxin, which was followed by orthogonal screens against two toxins that hijack the endolysosomal (diphtheria toxin) or retrograde (Shiga-like toxin 1) pathways to intoxicate cells. This led to the identification of the molecule C910 that induces the enlargement of EEA1-positive early endosomes associated with sorting defects of CNF1 and Shiga toxins to their trafficking pathways. C910 protects cells against eight bacterial AB toxins and the CNF1-mediated pathogenic Escherichia coli invasion. Interestingly, C910 reduces influenza A H1N1 and SARS-CoV-2 viral infection in vitro. Moreover, parenteral administration of C910 to mice resulted in its accumulation in lung tissues and a reduction in lethal influenza infection.
Published: 2022
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20. Considerable escape of SARS-CoV-2 Omicron to antibody neutralization

Author: Delphine Planas, Nell Saunders, Piet Maes, Florence Guivel-Benhassine, Cyril Planchais, Julian Buchrieser, William-Henry Bolland, Françoise Porrot, Isabelle Staropoli, Frederic Lemoine, Hélène Péré, David Veyer, Julien Puech, Julien Rodary, Guy Baele, Simon Dellicour, Joren Raymenants, Sarah Gorissen, Caspar Geenen, Bert Vanmechelen, Tony Wawina-Bokalanga, Joan Martí-Carreras, Lize Cuypers, Aymeric Sève, Laurent Hocqueloux, Thierry Prazuck, Félix A. Rey, Etienne Simon-Loriere, Timothée Bruel, Hugo Mouquet, Emmanuel André, Olivier Schwartz, Virus et Immunité - Virus and immunity (CNRS-UMR3569), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Vaccine Research Institute [Créteil, France] (VRI), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), École Doctorale Bio Sorbonne Paris Cité [Paris] (ED562 - BioSPC), Université Sorbonne Paris Cité (USPC)-Université Paris Cité (UPCité), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Immunologie humorale - Humoral Immunology, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Génomique fonctionnelle des tumeurs solides = Functional Genomics of Solid Tumors [CRC] (FunGeST), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Université libre de Bruxelles (ULB), University Hospitals Leuven [Leuven], Centre Hospitalier Régional d'Orléans (CHRO), Virologie Structurale - Structural Virology, Génomique évolutive des virus à ARN - Evolutionary genomics of RNA viruses, The Opera system was co-funded by Institut Pasteur and the Région ile de France (DIM1Health). Work in the O.S. laboratory is funded by Institut Pasteur, Urgence COVID-19 Fundraising Campaign of Institut Pasteur, Fondation pour la Recherche Médicale (FRM), ANRS, the Vaccine Research Institute (ANR-10-LABX-77), Labex IBEID (ANR-10-LABX-62-IBEID), ANR/FRM Flash Covid PROTEO-SARS-CoV-2 and IDISCOVR. Work in the UPBI is funded by grant ANR-10-INSB-04-01 and Région Ile-de-France program DIM1-Health. D.P. is supported by the Vaccine Research Institute. The H.M. laboratory is funded by the Institut Pasteur, the Milieu Intérieur Program (ANR-10-LABX-69-01), the INSERM, REACTing, EU (RECOVER) and Fondation de France (00106077) grants. The E.S.-L. laboratory is funded by Institut Pasteur, the INCEPTION program (Investissements d’Avenir grant ANR-16-CONV-0005) and the French Government’s Investissement d’Avenir programme, Laboratoire d’Excellence ‘Integrative Biology of Emerging Infectious Diseases’ (grant no. ANR-10-LABX-62-IBEID). G.B. acknowledges support from the Internal Funds KU Leuven under grant agreement C14/18/094, and the Research Foundation–Flanders (Fonds voor Wetenschappelijk Onderzoek–Vlaanderen, G0E1420N, G098321N). P.M. acknowledges support from a COVID-19 research grant of ‘Fonds Wetenschappelijk Onderzoek’/Research Foundation–Flanders (grant no. G0H4420N). S.D. is supported by the Fonds National de la Recherche Scientifique (FNRS, Belgium) and also acknowledges support from the Research Foundation–Flanders (Fonds voor Wetenschappelijk Onderzoek–Vlaanderen, G098321N) and from the European Union Horizon 2020 project MOOD (grant no. 874850)., ANR-10-LABX-0077,VRI,Initiative for the creation of a Vaccine Research Institute(2010), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-20-COVI-0059,PROTEO-SARS-CoV-2,Protéomique du SARS-CoV-2(2020), ANR-10-INBS-0004,France-BioImaging,Développment d'une infrastructure française distribuée coordonnée(2010), ANR-10-LABX-0069,MILIEU INTERIEUR,GENETIC & ENVIRONMENTAL CONTROL OF IMMUNE PHENOTYPE VARIANCE: ESTABLISHING A PATH TOWARDS PERSONALIZED MEDICINE(2010), ANR-16-CONV-0005,INCEPTION,Institut Convergences pour l'étude de l'Emergence des Pathologies au Travers des Individus et des populatiONs(2016), European Project: 874850,H2020-SC1-2019-Single-Stage-RTD,MOOD(2020), Virus et Immunité - Virus and immunity, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Vaccine Research Institute (VRI), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Institut Pasteur [Paris]-Université Paris Cité (UPCité), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)-École pratique des hautes études (EPHE), and European Project: 874850,MOOD
Subjects: MESH: Humans, MESH: Mutation, Multidisciplinary, MESH: ChAdOx1 nCoV-19, MESH: Neutralization Tests, MESH: Adult, MESH: Convalescence, MESH: Male, MESH: Antibodies, Monoclonal, MESH: Antibodies, Neutralizing, MESH: Belgium, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, MESH: COVID-19, MESH: Immunization, Secondary, MESH: SARS-CoV-2, MESH: Immune Evasion, MESH: BNT162 Vaccine, MESH: Phylogeny, MESH: Travel, MESH: Female, MESH: Antibodies, Viral
Abstract: The SARS-CoV-2 Omicron variant was first identified in November 2021 in Botswana and South Africa1-3. It has since spread to many countries and is expected to rapidly become dominant worldwide. The lineage is characterized by the presence of around 32 mutations in spike-located mostly in the N-terminal domain and the receptor-binding domain-that may enhance viral fitness and enable antibody evasion. Here we isolated an infectious Omicron virus in Belgium from a traveller returning from Egypt. We examined its sensitivity to nine monoclonal antibodies that have been clinically approved or are in development4, and to antibodies present in 115 serum samples from COVID-19 vaccine recipients or individuals who have recovered from COVID-19. Omicron was completely or partially resistant to neutralization by all monoclonal antibodies tested. Sera from recipients of the Pfizer or AstraZeneca vaccine, sampled five months after complete vaccination, barely inhibited Omicron. Sera from COVID-19-convalescent patients collected 6 or 12 months after symptoms displayed low or no neutralizing activity against Omicron. Administration of a booster Pfizer dose as well as vaccination of previously infected individuals generated an anti-Omicron neutralizing response, with titres 6-fold to 23-fold lower against Omicron compared with those against Delta. Thus, Omicron escapes most therapeutic monoclonal antibodies and, to a large extent, vaccine-elicited antibodies. However, Omicron is neutralized by antibodies generated by a booster vaccine dose. ispartof: NATURE vol:602 issue:7898 pages:671-+ ispartof: location:England status: published
Published: 2021
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21. COVID-19 outbreak in vaccinated patients from a haemodialysis unit: antibody titres as a marker of protection from infection

Author: Idris Boudhabhay, Alexandra Serris, Aude Servais, Delphine Planas, Aurélie Hummel, Bruno Guery, Perrine Parize, Claire Aguilar, Myriam Dao, Claire Rouzaud, Elsa Ferriere, Bertrand Knebelmann, Hamza Sakhi, Marianne Leruez, Dominique Joly, Olivier Schwartz, Fanny Lanternier, Timothée Bruel, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Santé et de la Recherche Médicale (INSERM), Service des Maladies infectieuses et tropicales [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service Néphrologie et transplantation rénale Adultes [CHU Necker], Virus et Immunité - Virus and immunity, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPC), Vaccine Research Institute (VRI), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service de néphrologie adultes [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Laboratoire de Virologie [CHU Necker], We thank William Henry Bolland for his critical reading of the manuscript and members of the Virus and Immunity Unit for discussions and help, Virus et Immunité - Virus and immunity (CNRS-UMR3569), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Vaccine Research Institute [Créteil, France] (VRI), and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)
Subjects: Transplantation, COVID-19 outbreak, hemodialysis, SARS-CoV-2, COVID-19, Viral Vaccines, Antibodies, Monoclonal, Humanized, Antibodies, Viral, Disease Outbreaks, Hemodialysis Units, Hospital, Nephrology, BNT162b2 mRNA vaccination, Renal Dialysis, Immunoglobulin G, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Humans, monoclonal antibodies, humoral response, BNT162 Vaccine, Retrospective Studies
Abstract: Background Patients on maintenance haemodialysis (HD) have an increased risk of severe coronavirus disease 2019 (COVID-19) and a reduced response to vaccines. Data are needed to identify immune correlates of protection in this population. Methods Following a COVID-19 outbreak among vaccinated patients in a HD unit, clinical data and serological response to BNT162b2 vaccine were retrospectively recorded. Results Among 53 patients present in the dialysis room, 14 were infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) alpha variant (COVID_Pos) and 39 were not. Compared with uninfected patients, COVID_Pos patients more frequently had additional causes of immunosuppression (50% versus 21%; P = .046) and were more often scheduled on the Monday–Wednesday–Friday (MWF) shift (86% versus 39%; P = .002). Moreover, COVID_Pos had lower anti-spike (S) immunoglobulin G (IgG) titres than uninfected patients {median 24 BAU/mL [interquartile range (IQR) 3–1163] versus 435 [99–2555]; P = .001} and lower neutralization titres [median 108 (IQR 17–224) versus 2483 (481–43 908); P = .007]. Anti-S and neutralization antibody titres are correlated (r = 0.92, P 284 BAU/mL got infected. Ten of 14 COVID_Pos patients were treated with casirivimab and imdevimab. No patient developed severe disease. Conclusions Anti-S IgG titre measured prior to exposure correlates to protection from SARS-CoV-2 infection in HD patients. BNT162b2 vaccination alone or in combination with monoclonal antibodies prevented severe COVID-19.
Published: 2021
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22. Targeting SARS-CoV-2 receptor-binding domain to cells expressing CD40 improves protection to infection in convalescent macaques

Author: Zhiqing Wang, Olivier Schwartz, Mathieu Surenaud, Mireille Centlivre, Gerard Zurawski, Julien Lemaitre, Léa Dupaty, Christine Lacabaratz, Yves Levy, Rodolphe Thiébaut, Sylvie van der Werf, Inga Szurgot, Romain Marlin, Véronique Godot, Severin Coleon, Aurélie Wiedemann, Giuseppe Pantaleo, Pauline Maisonnasse, Delphine Planas, Mélanie Prague, Catherine Chapon, Mario Gomez-Pacheco, Thibaut Naninck, Mathilde Galhaut, Anne-Sophie Gallouet, Jerome Ellis, Mariangela Cavarelli, Sandra Zurawski, Nidhal Kahlaoui, Roger Le Grand, Timothée Bruel, Francis Relouzat, Craig Fenwick, Nathalie Dereuddre-Bosquet, Sylvain Cardinaud, Raphael Ho Tsong Fang, Peter Liljeström, Vanessa Contreras, Immunologie des maladies virales, auto-immunes, hématologiques et bactériennes (IMVA-HB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Vaccine Research Institute (VRI), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Baylor Scott & White Charles A. Sammons Cancer Center [Dallas, TX, USA], Lausanne University Hospital, Université de Lausanne = University of Lausanne (UNIL), Karolinska Institutet [Stockholm], Virus et Immunité - Virus and immunity, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Génétique Moléculaire des Virus à ARN - Molecular Genetics of RNA Viruses (GMV-ARN (UMR_3569 / U-Pasteur_2)), Centre National de Référence des virus des infections respiratoires (dont la grippe) - National Reference Center Virus Influenzae [Paris] (CNR), Institut Pasteur [Paris]-Université Paris Cité (UPCité), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Statistics In System biology and Translational Medicine (SISTM), Inria Bordeaux - Sud-Ouest, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)- Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Bordeaux [Bordeaux], Hôpital Henri Mondor, Hôpital Albert Chenevier, The programme was funded by the Vaccine Research Institute via the ANR-10-LABX-77 grant. Studies in hu-mice model have been supported by ARN grant ANR-20-COV6-0004-01. The Infectious Disease Models and Innovative Therapies (IDMIT) research infrastructure is supported by the 'Programme Investissements d’Avenir', managed by the ANR under reference ANR-11-INBS-0008. The Fondation Bettencourt Schueller and the Region Ile-de-France contributed to the implementation of IDMIT’s facilities and imaging technologies. The NHP study received financial support from REACTing, the Fondation pour la Recherche Medicale (FRM, AM-CoV-Path) and the European Infrastructure TRANSVAC2 (730964) for implementation of in vivo imaging technologies an NHP immuno assays. The virus stock used in NHPs was obtained through the EVAg platform (https://www.european-virus-archive.com/), funded by H2020 (653316)., ANR-10-LABX-0077,VRI,Initiative for the creation of a Vaccine Research Institute(2010), ANR-20-COV6-0004,DC-CoVaC,Développement de vaccins anti-SARS-CoV-2(2020), ANR-11-INBS-0008,IDMIT,Infrastructure nationale pour la modélisation des maladies infectieuses humaines(2011), European Project: 730964, H2020, RIA,H2020-INFRAIA-2016-1,TRANSVAC2(2017), European Project: 653316,H2020,H2020-INFRAIA-2014-2015,EVAg(2015), University of Lausanne (UNIL), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Institut Pasteur [Paris], Vaccine Research Institute [Créteil, France] (VRI), Virus et Immunité - Virus and immunity (CNRS-UMR3569), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Centre National de Référence des virus des infections respiratoires (dont la grippe) - National Reference Center Virus Influenzae [Paris] (CNR - laboratoire coordonnateur), Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), DARMIGNY, SANDRINE, Laboratoires d'excellence - Initiative for the creation of a Vaccine Research Institute - - VRI2010 - ANR-10-LABX-0077 - LABX - VALID, Développement de vaccins anti-SARS-CoV-2 - - DC-CoVaC2020 - ANR-20-COV6-0004 - COVID-19 - VALID, Infrastructures - Infrastructure nationale pour la modélisation des maladies infectieuses humaines - - IDMIT2011 - ANR-11-INBS-0008 - INBS - VALID, European Vaccine Research and Development Infrastructure - TRANSVAC2 - - H2020, RIA2017-05-01 - 2022-04-30 - 730964 - VALID, and European Virus Archive goes global - EVAg - - H20202015-04-01 - 2019-03-31 - 653316 - VALID
Subjects: T-Lymphocytes, medicine.medical_treatment, [SDV]Life Sciences [q-bio], General Physics and Astronomy, Mice, 0302 clinical medicine, 030212 general & internal medicine, skin and connective tissue diseases, B-Lymphocytes, 0303 health sciences, Multidisciplinary, biology, Vaccination, 3. Good health, [SDV] Life Sciences [q-bio], Spike Glycoprotein, Coronavirus, Vaccines, Subunit, Antibody, Adjuvant, Protein vaccines, COVID-19 Vaccines, Science, Protein domain, Antigen-Presenting Cells, Virulence, Article, General Biochemistry, Genetics and Molecular Biology, Viral vector, 03 medical and health sciences, Protein Domains, medicine, Animals, Humans, CD40 Antigens, 030304 developmental biology, CD40, SARS-CoV-2, fungi, COVID-19, Convalescence, General Chemistry, Virology, body regions, Viral infection, Preclinical research, Reinfection, Mutation, Humanized mouse, biology.protein, Macaca
Abstract: Achieving sufficient worldwide vaccination coverage against SARS-CoV-2 will require additional approaches to currently approved viral vector and mRNA vaccines. Subunit vaccines may have distinct advantages when immunizing vulnerable individuals, children and pregnant women. Here, we present a new generation of subunit vaccines targeting viral antigens to CD40-expressing antigen-presenting cells. We demonstrate that targeting the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein to CD40 (αCD40.RBD) induces significant levels of specific T and B cells, with long-term memory phenotypes, in a humanized mouse model. Additionally, we demonstrate that a single dose of the αCD40.RBD vaccine, injected without adjuvant, is sufficient to boost a rapid increase in neutralizing antibodies in convalescent non-human primates (NHPs) exposed six months previously to SARS-CoV-2. Vaccine-elicited antibodies cross-neutralize different SARS-CoV-2 variants, including D614G, B1.1.7 and to a lesser extent B1.351. Such vaccination significantly improves protection against a new high-dose virulent challenge versus that in non-vaccinated convalescent animals., In this study, Marlin et al. provide insights into the potential use of subunit vaccines that induce a high level of protection against SARS-CoV-2 in animal models.
Published: 2021
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23. Kinetics of the Severe Acute Respiratory Syndrome Coronavirus 2 Antibody Response and Serological Estimation of Time Since Infection

Author: Pelleau, Stéphane, Woudenberg, Tom, Rosado, Jason, Donnadieu, Françoise, Garcia, Laura, Obadia, Thomas, Gardais, Soazic, Elgharbawy, Yasmine, Velay, Aurelie, Gonzalez, Maria, Nizou, Jacques Yves, Khelil, Nizar, Zannis, Konstantinos, Cockram, Charlotte, Merkling, Sarah Hélène, Meola, Annalisa, Kerneis, Solen, Terrier, Benjamin, de Seze, Jerome, Planas, Delphine, Schwartz, Olivier, Dejardin, François, Petres, Stéphane, von Platen, Cassandre, Pellerin, Sandrine Fernandes, Arowas, Laurence, de Facci, Louise Perrin, Duffy, Darragh, Cheallaigh, Clíona Ní, Dunne, Jean, Conlon, Niall, Townsend, Liam, Duong, Veasna, Auerswald, Heidi, Pinaud, Laurie, Tondeur, Laura, Backovic, Marija, Hoen, Bruno, Fontanet, Arnaud, Mueller, Ivo, Fafi-Kremer, Samira, Bruel, Timothée, White, Michael, Epidémiologie et Analyse des Maladies Infectieuses - Infectious Disease Epidemiology and Analytics, Institut Pasteur [Paris] (IP), Malaria : parasites et hôtes - Malaria : parasites and hosts, Santé publique : épidémiologie & sciences de l'information biomédicale (ED 393), Sorbonne Université (SU), Département de Biologie Computationnelle - Department of Computational Biology, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Strasbourg, Institut Mutualiste de Montsouris (IMM), Régulation spatiale des Génomes - Spatial Regulation of Genomes, Interactions Virus-Insectes - Insect-Virus Interactions (IVI), Virologie Structurale - Structural Virology, Epidémiologie et modélisation de la résistance aux antimicrobiens - Epidemiology and modelling of bacterial escape to antimicrobials (EMAE), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Department of Internal Medicine, National Referral Center for Rare Systemic Autoimmune Diseases, Assistance Publique Hôpitaux de Paris-Centre (APHP-CUP), Université de Paris, Paris, France, Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), CIC Strasbourg (Centre d’Investigation Clinique Plurithématique (CIC - P) ), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Nouvel Hôpital Civil de Strasbourg-Hôpital de Hautepierre [Strasbourg], Virus et Immunité - Virus and immunity (CNRS-UMR3569), Plateforme technologique Production et purification de protéines recombinantes – Production and Purification of Recombinant Proteins Technological Platform (PPR), Centre de Recherche Translationnelle - Center for Translational Science (CRT), Investigation Clinique et d’Accès aux Ressources Biologiques (Plate-forme) - Clinical Investigation and Access to BioResources (ICAReB), Immunologie Translationnelle - Translational Immunology lab, St James's University Hospital, Leeds Teaching Hospitals NHS Trust, Trinity College Dublin, Institut Pasteur du Cambodge, Réseau International des Instituts Pasteur (RIIP), Epidémiologie des Maladies Emergentes - Emerging Diseases Epidemiology, Pasteur-Cnam Risques infectieux et émergents (PACRI), Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), Direction de la recherche médicale de l'Institut Pasteur, Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), The Walter and Eliza Hall Institute of Medical Research (WEHI), University of Melbourne, Vaccine Research Institute [Créteil, France] (VRI), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), This work was supported by the European Research Council (MultiSeroSurv ERC Starting Grant 852373, MW), l’Agence Nationale de la Recherche and Fondation pour la Recherche Médicale (CorPopImm, MW), and the Institut Pasteur International Network (CoronaSeroSurv, MW). JR was supported by the Pasteur Paris University (PPU) International PhD Program. CC was supported by the European Research Council 771813. MB, AL and HA were supported by the « URGENCE COVID-19 » fundraising campaign of Institut Pasteur. HA is supported by Centre for International Migration and Development. NC and CNC are part-funded by a Science Foundation Ireland (SFI) grant, Grant Code 20/SPP/3685. LT has been awarded the Irish ClinicalAcademic Training (ICAT) Programme, supported by the Wellcome Trust and the Health Research Board (Grant Number 203930/B/16/Z), the Health Service Executive, National Doctors Training and Planning and the Health and Social Care, Research and Development Division, Northern Ireland (https://icatprogramme.org/). MB and AM were supported by Institut Pasteur TaskForce funding (TooLab project). IM is supported by a NHMRC Principal Research Fellowship. SFK lab is funded by Strasbourg University Hospitals (SeroCoV-HUS, PRI 7782), the Agence Nationale de la Recherche (ANR-18-CE17-0028), Laboratoire d'Excellence TRANSPLANTEX (ANR-11-LABX-0070_TRANSPLANTEX), and Institut National de la Santé et de la Recherche Médicale (UMR_S1109)., ANR-20-COVI-0052,CorPopImm,Évaluer l'immunité contre SARS-CoV-2 à l'échelle de la population grâce aux tests sérologiques(2020), ANR-18-CE17-0028,HuMABK,Les anticorps monoclonaux humains : une Nouvelle approche thérapeutique contre l'infection par le virus BK et les maladies associées(2018), ANR-11-LABX-0070,TRANSPLANTEX,Nouveaux loci d'histocompatibilité/biomarqueurs en transplantation humaine: de la découverte à l'app(2011), European Project: 852373,ERC-2019-STG,MultiSeroSurv(2020), European Project: 771813,ERC-2017-COG,SynarchiC(2018), Institut Pasteur [Paris], Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC), Virus et Immunité - Virus and immunity, Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université (HESAM)-HESAM Université (HESAM)-Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université (HESAM)-HESAM Université (HESAM), HESAM Université (HESAM), Vaccine Research Institute (VRI), and HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM)
Subjects: Male, Aucun, Antibodies, Viral, time since infection, MESH: Aged, 80 and over, Antibody Specificity, Seroepidemiologic Studies, MESH: COVID-19, Aged, 80 and over, MESH: Immunoglobulin G, MESH: Aged, MESH: Middle Aged, seroprevalence, MESH: Kinetics, Middle Aged, MESH: Antibody Formation, AcademicSubjects/MED00290, MESH: Young Adult, surveillance, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, France, Adult, antibody kinetics, Adolescent, SARS-SoV-2, Sensitivity and Specificity, Young Adult, Major Article, Humans, Serologic Tests, MESH: SARS-CoV-2, MESH: Antibody Specificity, Aged, MESH: Adolescent, MESH: Humans, MESH: Seroepidemiologic Studies, SARS-CoV-2, MESH: Serologic Tests, COVID-19, MESH: Adult, MESH: Male, MESH: Sensitivity and Specificity, MESH: France, Kinetics, sero-prevalence, Immunoglobulin G, Antibody Formation, MESH: Female, MESH: Antibodies, Viral
Abstract: Background Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces a complex antibody response that varies by orders of magnitude between individuals and over time. Methods We developed a multiplex serological test for measuring antibodies to 5 SARS-CoV-2 antigens and the spike proteins of seasonal coronaviruses. We measured antibody responses in cohorts of hospitalized patients and healthcare workers followed for up to 11 months after symptoms. A mathematical model of antibody kinetics was used to quantify the duration of antibody responses. Antibody response data were used to train algorithms for estimating time since infection. Results One year after symptoms, we estimate that 36% (95% range, 11%–94%) of anti-Spike immunoglobulin G (IgG) remains, 31% (95% range, 9%–89%) anti-RBD IgG remains, and 7% (1%–31%) of anti-nucleocapsid IgG remains. The multiplex assay classified previous infections into time intervals of 0–3 months, 3–6 months, and 6–12 months. This method was validated using data from a seroprevalence survey in France, demonstrating that historical SARS-CoV-2 transmission can be reconstructed using samples from a single survey. Conclusions In addition to diagnosing previous SARS-CoV-2 infection, multiplex serological assays can estimate the time since infection, which can be used to reconstruct past epidemics., Longitudinal follow-up of individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reveals differences in the duration of antibodies to multiple antigens. Mathematical models of antibody waning and statistical algorithms can estimate an individual’s time since SARS-CoV-2 infection, and previous transmission waves in a population.
Published: 2021
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24. Release of infectious virus and cytokines in nasopharyngeal swabs from individuals infected with non-alpha or alpha SARS-CoV-2 variants: an observational retrospective study

Author: Monel, Blandine, Planas, Delphine, Grzelak, Ludivine, Smith, Nikaïa, Robillard, Nicolas, Staropoli, Isabelle, Goncalves, Pedro, Porrot, Françoise, Guivel-Benhassine, Florence, Guinet, Nathalie Demory, Rodary, Julien, Puech, Julien, Euzen, Victor, Bélec, Laurent, Orvoen, Galdric, Nunes, Léa, Moulin, Véronique, Fourgeaud, Jacques, Wack, Maxime, Imbeaud, Sandrine, Campagne, Pascal, Duffy, Darragh, Di Santo, James, Bruel, Timothée, Péré, Hélène, Veyer, David, Schwartz, Olivier, Virus et Immunité - Virus and immunity (CNRS-UMR3569), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Vaccine Research Institute [Créteil, France] (VRI), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Université Paris Cité (UPCité), Immunologie Translationnelle - Translational Immunology lab, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Immunité Innée - Innate Immunity, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Hôpital Vaugirard-Gabriel Pallez, Hôpital Corentin Celton [Issy-les-Moulineaux], Laboratoire de Virologie [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Work in OS lab is funded by Institut Pasteur, Urgence COVID-19 Fundraising Campaign of Institut Pasteur, ANRS, the Vaccine Research Institute (ANR-10-LABX-77), Labex IBEID (ANR-10-LABX-62-IBEID), ANR/FRM Flash Covid PROTEO-SARS-CoV-2 and IDISCOVR, Fondation pour la Recherche Médicale. DP is supported by the Vaccine Research Institute. LG is supported by the French Ministry of Higher Education, Research and Innovation. DD and JDS are funded by the ANR-20-COVI-0053 grant., We thank Maaran Michael Rajah, Nicoletta Casartelli, Michael White and Jeremy Dufloo for discussion and critical reading of the manuscript. We thank AGEPS, Assistance Publique - Hôpitaux de Paris, for providing the RDTs. We thank the patients who participated in the study, the clinical staff involved in their management, Théo Hirsch for stimulating discussions. We thank members of the Virus and Immunity Unit for discussion and help, Nathalie Aulner and the UtechS Photonic BioImaging (UPBI) core facility (Institut Pasteur), a member of the France BioImaging network, for image acquisition and analysis, and Cyril Planchais & Hugo Mouquet for the kind gift of mAb48., ANR-10-LABX-0077,VRI,Initiative for the creation of a Vaccine Research Institute(2010), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-20-COVI-0059,PROTEO-SARS-CoV-2,Protéomique du SARS-CoV-2(2020), ANR-20-COVI-0053,CoVarImm,Variation de la réponse immune systémique et muqueuse pendant l'infection par le SRAS-CoV-2 et la convalescence(2020), Virus et Immunité - Virus and immunity, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Vaccine Research Institute (VRI), Institut Pasteur [Paris]-Université Paris Cité (UPCité), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), École pratique des hautes études (EPHE), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Université de Paris (UP), Institut Pasteur [Paris], Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP)
Subjects: Adult, Male, Nasal swabs, Medicine (General), variants, Research paper, SARS-CoV-2, COVID-19, Middle Aged, Antibodies, Viral, Immunoglobulin A, infectious particles, R5-920, Immunoglobulin G, Nasopharynx, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Medicine, Cytokines, Humans, Female, Aged, Retrospective Studies
Abstract: Background: The dynamics of SARS-CoV-2 alpha variant shedding and immune responses at the nasal mucosa remain poorly characterised. Methods: We measured infectious viral release, antibodies and cytokines in 426 PCR+ nasopharyngeal swabs from individuals harboring non-alpha or alpha variants. Findings: With both lineages, viral titers were variable, ranging from 0 to >106 infectious units. Rapid antigenic diagnostic tests were positive in 94% of samples with infectious virus. 68 % of individuals carried infectious virus within two days after onset of symptoms. This proportion decreased overtime. Viable virus was detected up to 14 days. Samples containing anti-spike IgG or IgA did not generally harbor infectious virus. Ct values were slightly but not significantly lower with alpha. This variant was characterized by a fast decrease of infectivity overtime and a marked release of 13 cytokines (including IFN-b, IP-10 and IL-10). Interpretation: The alpha variant displays modified viral decay and cytokine profiles at the nasopharyngeal mucosae during symptomatic infection. Funding: This retrospective study has been funded by Institut Pasteur, ANRS, Vaccine Research Institute, Labex IBEID, ANR/FRM and IDISCOVR, Fondation pour la Recherche Médicale.
Published: 2021
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25. Bystander CD4 T-cell death is inhibited by broadly neutralizing anti-HIV antibodies only at levels blocking cell-to-cell viral transmission

Author: Xiaoyu Luo, Olivier Schwartz, Hugo Mouquet, Warner C. Greene, Gladstone Institutes [San Francisco], Immunologie humorale - Humoral Immunology, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Virus et Immunité - Virus and immunity, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Département de Virologie - Department of Virology, Institut Pasteur [Paris] (IP), University of California [San Francisco] (UC San Francisco), University of California (UC), This research was supported by the National Institutes of Health, United States (R01DA044605, P0110018714, P30AI027763, and S10 RR028962), and Institut Pasteur, France, and INSERM, France. We also gratefully acknowledge funding support from the James B. Pendleton Charitable Trust., The authors acknowledge David N. Levy of New York University for the multiple-round NLENG1-IRES HIV reporter clones and Oliver T. Keppler for HIV-1∗.GFP proviral DNA. We acknowledge for technical support from the Gladstone Flow Cytometry Core, including that of Jane Srivastava and Nandhini Rahman. We thank Valérie Lorin (Humoral Immunology laboratory, Institut Pasteur) for the production of HIV bNAb and control antibodies. We thank Jason Neidleman for editorial assistance and Robin Givens for administrative assistance., Ziani, Isma, and Virus et Immunité - Virus and immunity (CNRS-UMR3569)
Subjects: bNAb, broadly neutralizing anti-HIV antibody, CD4-Positive T-Lymphocytes, Programmed cell death, Accelerated Communication, cell–cell interaction, IgG, immunoglobulin G, HIV Infections, HIV Antibodies, Biochemistry, Virus, Cell–cell interaction, FACS, fluorescence-activated cell sorting, Bystander effect, Humans, Molecular Biology, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, biology, pyroptosis, Pyroptosis, apoptosis, HIV, Bystander Effect, Cell Biology, HIV envelope protein, Antibodies, Neutralizing, Virology, infection, HLAC, human lymphoid aggregate culture, cell death, CMAC, 7-amino-4-chloromethylcoumarin, Apoptosis, broadly neutralizing anti-HIV antibodies, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, HIV-1, biology.protein, Antibody, cell-free virus transmission
Abstract: International audience; The progressive loss of CD4+ T cells during HIV infection of lymphoid tissues involves both the apoptotic death of activated and productively infected CD4 T cells and the pyroptotic death of large numbers of resting and abortively infected bystander CD4 T cells. HIV spreads both through cellular release of virions and cell-to-cell transmission involving the formation of virological synapses. Cell-to-cell transmission results in high-level transfer of large quantities of virions to the target cell exceeding that achieved with cell-free virions. Broadly neutralizing anti-HIV antibodies (bNAbs) binding to HIV envelope protein capably block cell-free virus spread, and when added at higher concentrations can also interdict cell-to-cell transmission. Exploiting these distinct dose–response differences, we now show that four different bNAbs block the pyroptotic death of bystander cells, but only when added at concentrations sufficient to block cell-to-cell transmission. These findings further support the conclusion that HIV killing of abortively infected bystander CD4 T cells requires cell-to-cell transfer of virions. As bNAbs attract more interest as potential therapeutics, it will be important to consider the higher concentrations of these antibodies required to block the inflammatory death of bystander CD4 T cells.
Published: 2021
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26. The FDA-approved drug Auranofin has a dual inhibitory effect on SARS-CoV-2 entry and NF-κB signaling

Author: Emmanuel Laplantine, Christine Chable-Bessia, Anne Oudin, Jitendryia Swain, Adèle Soria, Peggy Merida, Manon Gourdelier, Sarra Mestiri, Indira Besseghe, Erwan Bremaud, Aymeric Neyret, Sebastien Lyonnais, Cyril Favard, Philippe Benaroch, Mathieu Hubert, Olivier Schwartz, Maryse Guerin, Anne Danckaert, Elaine Del Nery, Delphine Muriaux, Robert Weil, Centre d'Immunologie et des Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre d’études des Maladies Infectieuses et Pharmacologie Anti-Infectieuse - [Montpellier] (CEMIPAI), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Institut de génétique humaine (IGH), Institut de Recherche en Infectiologie de Montpellier (IRIM), BioImaging Cell and Tissue Core Facility (PICT-IBiSA), Institut Curie [Paris], Institut Curie, PSL Research University, INSERM U932., Institut Pasteur [Paris], Virologie (CNRS - UMR3569), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Virus et Immunité - Virus and immunity, Vaccine Research Institute (VRI), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases [IHU ICAN], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), BioImagerie Photonique – Photonic BioImaging (UTechS PBI), Institut Pasteur [Paris]-Université Paris Cité (UPCité), Immunité et cancer (U932), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Laplantine, Emmanuel, Développment d'une infrastructure française distribuée coordonnée - - France-BioImaging2010 - ANR-10-INBS-0004 - INBS - VALID, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Institut Pasteur [Paris] (IP), Institut Pasteur, UTechS Photonic BioImaging (PBI), a member of the national infrastructure France-BioImaging supported by the French National Research Agency (ANR-10-INBS-04), kindly acknowledges the financial support of the Région Ile-de France (program DIM1Health) and the Institut Pasteur. This study was supported by the CNRS and Montpellier University through a Montpellier Université d’Excellence (MUSE) support, and the French Agency for Research through the Fondation de la Recherche Médicale (ANR COVID19 to DM) and Cancéropôle Ile-de-France (Emergence Grant, to EL)., ANR-10-INBS-0004,France-BioImaging,Développment d'une infrastructure française distribuée coordonnée(2010), Virus et Immunité - Virus and immunity (CNRS-UMR3569), and Vaccine Research Institute [Créteil, France] (VRI)
Subjects: Chemistry, Multidisciplinary, Molecular biology, [SDV]Life Sciences [q-bio], [SDV.BC.BC] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Medical biochemistry, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, Biochemistry
Abstract: International audience; Patients with severe COVID-19 show an altered immune response that fails to control the viral spread and suffer from exacerbated inflammatory response, which eventually can lead to death. A major challenge is to develop an effective treatment for COVID-19. NF-κB is a major player in innate immunity and inflammatory process. By a high-throughput screening approach, we identified FDA-approved compounds that inhibit the NF-κB pathway and thus dampen inflammation. Among these, we show that Auranofin prevents post-translational modifications of NF-κB effectors and their recruitment into activating complexes in response to SARS-CoV-2 infection or cytokine stimulation. In addition, we demonstrate that Auranofin counteracts several steps of SARS-CoV-2 infection. First, it inhibits a raft-dependent endocytic pathway involved in SARS-CoV-2 entry into host cells; Second, Auranofin alters the ACE2 mobility at the plasma membrane. Overall, Auranofin should prevent SARS-CoV-2 infection and inflammatory damages, offering new opportunities as a repurposable drug candidate to treat COVID-19.
Published: 2022
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27. SARS-CoV-2 Alpha, Beta, and Delta variants display enhanced Spike-mediated syncytia formation

Author: Mathieu Hubert, Jérémy Dufloo, Rémy Robinot, Hugo Mouquet, Olivier Schwartz, Ludivine Grzelak, Nell Saunders, Elodie Bishop, Françoise Porrot, Delphine Planas, Maaran Michael Rajah, Julian Buchrieser, Lisa A. Chakrabarti, Marija Zivaljic, Alice Bongers, Stacy Gellenoncourt, Florence Guivel-Benhassine, Cyril Planchais, Virus et Immunité - Virus and immunity, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Université Paris Cité (UPCité), Vaccine Research Institute (VRI), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Sorbonne Université (SU), Neurobiologie intégrative des Systèmes cholinergiques / Integrative Neurobiology of Cholinergic Systems (NISC), Institut Pasteur [Paris]-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Ecole doctorale Cerveau Cognition et Comportement [Paris] (ED 158 - 3C), Immunologie humorale - Humoral Immunology, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Work in OS lab is funded by Institut Pasteur, Urgence COVID-19 Fundraising Campaign of Institut Pasteur, ANRS, the Vaccine Research Institute (ANR-10-LABX-77), Fondation Pour la Recherche Médicale (FRM), Labex IBEID (ANR-10-LABX62-IBEID), ANR/FRM Flash Covid PROTEO-SARS-CoV-2, ANR CoronaMito AAP RA-COVID-19 V14, and IDISCOVR. Work in UPBI is funded by grant ANR-10-INSB-04-01 and Région Ile-de-France program DIM1-Health. MMR and MZ are supported by the Pasteur-Paris University (PPU) International Doctoral Program. MMR is also supported by Institut Pasteur Department of Virology 'Bourse de Soudure' fellowship. DP is supported by the Vaccine Research Institute. LG is supported by the French Ministry of Higher Education, Research and Innovation. EB is supported by the Medecine-Sciences ENS-PSL Program. HM laboratory is funded by the Institut Pasteur, the Milieu Intérieur Program (ANR-10-LABX-69- 01), the INSERM, REACTing, EU (RECOVER), and Fondation de France (#00106077) grants., We thank members of the Virus and Immunity Unit for helpful discussions, Dr. Nicoletta Casartelli for her critical reading of the manuscript, and Nathalie Aulner and the UtechS Photonic BioImaging (UPBI) core facility (Institut Pasteur), a member of the France BioImaging network, for image acquisition and analysis support., ANR-10-LABX-0077,VRI,Initiative for the creation of a Vaccine Research Institute(2010), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-20-COVI-0059,PROTEO-SARS-CoV-2,Protéomique du SARS-CoV-2(2020), ANR-21-CO14-0007,CoronaMito,Conséquences de l'infection par le SRAS-CoV-2 sur la fonction mitochondriale(2021), ANR-10-INBS-0004,France-BioImaging,Développment d'une infrastructure française distribuée coordonnée(2010), ANR-10-LABX-0069,MILIEU INTERIEUR,GENETIC & ENVIRONMENTAL CONTROL OF IMMUNE PHENOTYPE VARIANCE: ESTABLISHING A PATH TOWARDS PERSONALIZED MEDICINE(2010), Virus et Immunité - Virus and immunity (CNRS-UMR3569), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Vaccine Research Institute [Créteil, France] (VRI), Institut Pasteur [Paris] (IP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Ziani, Isma, Laboratoires d'excellence - Initiative for the creation of a Vaccine Research Institute - - VRI2010 - ANR-10-LABX-0077 - LABX - VALID, Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - VALID, Protéomique du SARS-CoV-2 - - PROTEO-SARS-CoV-22020 - ANR-20-COVI-0059 - COVID-19 - VALID, Conséquences de l'infection par le SRAS-CoV-2 sur la fonction mitochondriale - - CoronaMito2021 - ANR-21-CO14-0007 - COVID-19 - VALID, Développment d'une infrastructure française distribuée coordonnée - - France-BioImaging2010 - ANR-10-INBS-0004 - INBS - VALID, and Laboratoires d'excellence - GENETIC & ENVIRONMENTAL CONTROL OF IMMUNE PHENOTYPE VARIANCE: ESTABLISHING A PATH TOWARDS PERSONALIZED MEDICINE - - MILIEU INTERIEUR2010 - ANR-10-LABX-0069 - LABX - VALID
Subjects: fusion, coronavirus, MESH: Spike Glycoprotein, Coronavirus, MESH: Angiotensin-Converting Enzyme 2, medicine.disease_cause, Virus Replication, Giant Cells, SARS‐CoV‐2, MESH: Antibodies, Monoclonal, MESH: Giant Cells, MESH: Chlorocebus aethiops, Chlorocebus aethiops, MESH: Animals, Receptor, Coronavirus, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Syncytium, Strain (chemistry), General Neuroscience, Antibodies, Monoclonal, Articles, Transmembrane protein, Microbiology, Virology & Host Pathogen Interaction, Cell biology, MESH: HEK293 Cells, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Spike Glycoprotein, Coronavirus, MESH: Caco-2 Cells, Angiotensin-Converting Enzyme 2, MESH: Mutation, medicine.drug_class, Immunology, Alpha (ethology), MESH: Vero Cells, Biology, Monoclonal antibody, General Biochemistry, Genetics and Molecular Biology, Article, Cell Line, medicine, Animals, Humans, MESH: SARS-CoV-2, Beta (finance), syncytia, Molecular Biology, Vero Cells, MESH: Humans, General Immunology and Microbiology, SARS-CoV-2, MESH: Virus Replication, spike, MESH: Cell Line, HEK293 Cells, Mutation, Caco-2 Cells
Abstract: Severe COVID‐19 is characterized by lung abnormalities, including the presence of syncytial pneumocytes. Syncytia form when SARS‐CoV‐2 spike protein expressed on the surface of infected cells interacts with the ACE2 receptor on neighboring cells. The syncytia forming potential of spike variant proteins remain poorly characterized. Here, we first assessed Alpha (B.1.1.7) and Beta (B.1.351) spread and fusion in cell cultures, compared with the ancestral D614G strain. Alpha and Beta replicated similarly to D614G strain in Vero, Caco‐2, Calu‐3, and primary airway cells. However, Alpha and Beta formed larger and more numerous syncytia. Variant spike proteins displayed higher ACE2 affinity compared with D614G. Alpha, Beta, and D614G fusion was similarly inhibited by interferon‐induced transmembrane proteins (IFITMs). Individual mutations present in Alpha and Beta spikes modified fusogenicity, binding to ACE2 or recognition by monoclonal antibodies. We further show that Delta spike also triggers faster fusion relative to D614G. Thus, SARS‐CoV‐2 emerging variants display enhanced syncytia formation., Spike protein mutations expressed by emerging SARS‐CoV‐2 variants‐of‐concern differentially affect host cell‐to‐cell fusion, ACE2 receptor binding, and antibody escape.
Published: 2021
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28. Characteristics Associated with Olfactory and Taste Disorders in COVID-19

Author: Ludivine Grzelak, Charlotte Renaudat, Arnaud Fontanet, Timothée Bruel, Bruno Hoen, Marie-Noëlle Ungeheuer, Olivier Schwartz, Yoann Madec, Laura Tondeur, Simon Galmiche, Isabelle Cailleau, Isabelle Staropoli, Sandrine Fernandes Pellerin, Epidémiologie des Maladies Emergentes - Emerging Diseases Epidemiology, Université Paris Cité (UPCité)-Pasteur-Cnam Risques infectieux et émergents (PACRI), Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Paris Cité (UPCité)-Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), Virus et Immunité - Virus and immunity (CNRS-UMR3569), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Université Paris Cité (UPCité), Direction de la recherche médicale de l'Institut Pasteur, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Investigation Clinique et d’Accès aux Ressources Biologiques (Plate-forme) - Clinical Investigation and Access to BioResources (ICAReB), Centre de Recherche Translationnelle - Center for Translational Science (CRT), Vaccine Research Institute [Créteil, France] (VRI), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Pasteur-Cnam Risques infectieux et émergents (PACRI), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Paris Cité (UPCité), This work was supported by Institut Pasteur, and several laboratories participating in the study received funding from the Labex IBEID (ANR-10-LABX-62-IBEID), REACTing, and the INCEPTION project (PIA/ANR-16-CONV-0005) for studies focusing on emerging viruses. OS lab is funded by Institut Pasteur, ANRS, Sidaction, the Vaccine Research Institute (ANR-10-LABX-77), 'TIMTAMDEN' ANR-14-CE14-0029, 'CHIKV-Viro-Immuno' ANR-14-CE14-0015-01, and the Gilead HIV cure program. L.G. is supported by the French Ministry of Higher Education, Research, and Innovation., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-08-BLAN-0046,REACTING,Reactivity of inorganic radicals in aqueous solution(2008), ANR-16-CONV-0005,INCEPTION,Institut Convergences pour l'étude de l'Emergence des Pathologies au Travers des Individus et des populatiONs(2016), ANR-10-LABX-0077,VRI,Initiative for the creation of a Vaccine Research Institute(2010), ANR-14-CE14-0029,TIMTAMDEN,Rôle des récepteurs TIM et TAM dans l'infection des cellules cibles par le virus de la dengue(2014), ANR-14-CE14-0015,CHIKV-Viro-Immuno,Multiplication et Relation avec l'hôte du virus Chikungunya(2014), Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Paris Cité (UPCité)-Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM), Virus et Immunité - Virus and immunity, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut Pasteur [Paris]-Université Paris Cité (UPCité), and Vaccine Research Institute (VRI)
Subjects: Adult, medicine.medical_specialty, Adolescent, Coronavirus disease 2019 (COVID-19), Epidemiology, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Anosmia, Antibodies, Viral, Olfaction Disorders, Taste Disorders, Young Adult, Risk Factors, Internal medicine, Humans, Medicine, In patient, Child, Retrospective Studies, Original Paper, business.industry, Headache, Outbreak, COVID-19, Retrospective cohort study, Ageusia, Severe acute respiratory syndrome coronavirus-2, Taste disorder, Neurology (clinical), medicine.symptom, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Introduction: Olfactory and taste disorders (OTDs) have been reported in COVID-19 caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the mechanisms of which remain unclear. We conducted a detailed analysis of OTDs as part of 2 seroepidemiological investigations of COVID-19 outbreaks. Methods: Two retrospective cohort studies were conducted in a high school and primary schools of Northern France following a COVID-19 epidemic in February-March 2020. Students, their relatives, and school staff were included. Anti-SARS-CoV-2 antibodies were identified using a flow-cytometry-based assay detecting anti-S IgG. Results: Among 2,004 participants (median [IQR] age: 31 [11–43] years), 303 (15.2%) tested positive for SARS-CoV-2 antibodies. OTDs were present in 91 (30.0%) and 92 (30.3%) of them, respectively, and had 85.1 and 78.0% positive predictive values for SARS-CoV-2 infection, respectively. In seropositive participants, OTDs were independently associated with an age above 18 years, female gender, fatigue, and headache. Conclusion: This study confirms the higher frequency of OTDs in females than males and adults than children. Their high predictive value for the diagnosis of COVID-19 suggests that they should be systematically searched for in patients with respiratory symptoms, fever, or headache. The association of OTDs with headache, not previously reported, suggests that they share a common mechanism, which deserves further investigation.
Published: 2021
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29. A monocyte/dendritic cell molecular signature of SARS-CoV-2-related multisystem inflammatory syndrome in children with severe myocarditis

Author: Cécile Masson, Aurélien Corneau, Florence Moulin, Ghaith Abdessalem, Pedro Gonçalves, Marianne Leruez, James P. Di Santo, Mathie Lorrot, Julie Toubiana, Julien Haroche, Camille Bruneau, Isabelle Melki, Bruno Charbit, Zahra Belhadjer, Loïc de Pontual, Camille de Cevins, Brigitte Bader Meunier, Alain Fischer, Victor Garcia-Paredes, Brieuc P. Perot, Marine Luka, Damien Bonnet, Quentin Riller, Nikaïa Smith, Slimane Allali, Sonia Meynier, Aude Magérus, Christele Gras Leguen, Shen-Ying Zhang, Olivier Schwartz, Jean-Laurent Casanova, Frédéric Rieux-Laucat, Nicolas Cagnard, Francesco Carbone, Tinhinane Fali, Mélanie Parisot, Mickaël M. Ménager, Maxime Beretta, Mohammed Zarhrate, Christine Bole-Feysot, Vithura Pirabarakan, Ludivine Grzelak, Mehdi Oualha, Darragh Duffy, Laura Barnabei, Hugo Mouquet, Maxime Batignes, Alexandre Boullé, Boris Sorin, Marie-Claude Stolzenberg, Inflammatory Responses and Transcriptomic Networks in diseases (Equipe Inserm U1163), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Sanofi Aventis R&D [Chilly-Mazarin], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Immunologie Translationnelle - Translational Immunology lab, Institut Pasteur [Paris] (IP), Immunogenetics of pediatric autoimmune diseases (Equipe Inserm U1163), Cytometrie et Biomarqueurs – Cytometry and Biomarkers (UTechS CB), Immunologie humorale - Humoral Immunology, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Virus et Immunité - Virus and immunity (CNRS-UMR3569), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Immunité Innée - Innate Immunity, Structure Fédérative de Recherche Necker (SFR Necker - UMS 3633 / US24), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Cytométrie Pitié-Salpêtrière (PASS-CYPS), Unité Mixte de Service Production et Analyse de données en Sciences de la vie et en Santé (PASS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Human genetics of infectious diseases : Mendelian predisposition (Equipe Inserm U1163), Rockefeller University [New York], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre d'Immunologie et des Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), AP-HP Hôpital universitaire Robert-Debré [Paris], Université Paris Cité (UPCité), CHU Trousseau [APHP], Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), Hôpital Jean Verdier [AP-HP], Université Paris 13 (UP13), Collège de France (CdF (institution)), Biodiversité et Epidémiologie des Bactéries pathogènes - Biodiversity and Epidemiology of Bacterial Pathogens, ANR-18-IDEX-0001,Université de Paris,Université de Paris(2018), ANR-17-EURE-0013,GENE,Génétique et Epigénétique Nouvelle Ecole(2017), ANR-18-RHUS-0010,ATRACTION,Autoimmunity/inflammation Through Rnaseq Analysis at the single Cell level for Therapeutic Innovation(2018), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC), Institut Pasteur [Paris], Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Virus et Immunité - Virus and immunity, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPC), and Université Paris Cité (UPC)
Subjects: Adult, Vascular Endothelial Growth Factor A, Chemokine, Myocarditis, medicine.medical_treatment, [SDV]Life Sciences [q-bio], MIS-C, Monocytes, chemistry.chemical_compound, Viewpoint, scRNA-seq, medicine, otorhinolaryngologic diseases, Humans, Kawasaki Disease, Child, Connective Tissue Diseases, biology, business.industry, SARS-CoV-2, Monocyte, NF-kappa B, COVID-19, General Medicine, Dendritic Cells, Gene signature, medicine.disease, Pathophysiology, Systemic Inflammatory Response Syndrome, Vascular endothelial growth factor, medicine.anatomical_structure, Cytokine, chemistry, TNF-α and NF-κB signaling, Immunology, biology.protein, Cytokines, Tumor necrosis factor alpha, lack of responses to type I and type II IFN secretion, Clinical and Translational Article, Chemokines, myocarditis, business, PIMS-TS
Abstract: Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children is generally milder than in adults, but a proportion of cases result in hyperinflammatory conditions often including myocarditis. Methods To better understand these cases, we applied a multiparametric approach to the study of blood cells of 56 children hospitalized with suspicion of SARS-CoV-2 infection. Plasma cytokine and chemokine levels and blood cellular composition were measured, alongside gene expression at the bulk and single-cell levels. Findings The most severe forms of multisystem inflammatory syndrome in children (MIS-C) related to SARS-CoV-2 that resulted in myocarditis were characterized by elevated levels of pro-angiogenesis cytokines and several chemokines. Single-cell transcriptomics analyses identified a unique monocyte/dendritic cell gene signature that correlated with the occurrence of severe myocarditis characterized by sustained nuclear factor κB (NF-κB) activity and tumor necrosis factor alpha (TNF-α) signaling and associated with decreased gene expression of NF-κB inhibitors. We also found a weak response to type I and type II interferons, hyperinflammation, and response to oxidative stress related to increased HIF-1α and Vascular endothelial growth factor (VEGF) signaling. Conclusions These results provide potential for a better understanding of disease pathophysiology. Funding Agence National de la Recherche (Institut Hospitalo-Universitaire Imagine, grant ANR-10-IAHU-01; Recherche Hospitalo-Universitaire, grant ANR-18-RHUS-0010; Laboratoire d’Excellence ‘‘Milieu Intérieur,” grant ANR-10-LABX-69-01; ANR-flash Covid19 “AIROCovid” and “CoVarImm”), Institut National de la Santé et de la Recherche Médicale (INSERM), and the “URGENCE COVID-19” fundraising campaign of Institut Pasteur., Graphical abstract, Context and significance Children with SARS-CoV-2 infection were initially thought to have only mild COVID-19 symptoms. However, several weeks into the first wave of SARS-CoV-2 infections, there was a surge of a postacute pathology called multisystem inflammatory syndrome in children (MIS-C). The authors recruited a cohort of children with suspicion of SARS-CoV-2 infection and uncovered hyperinflammation, hypoxic conditions, exacerbation of TNF-α signaling via NF-κB, and absence of responses to type I and type II IFN secretion in the most severe forms of MIS-C with severe myocarditis. This work led the authors to identify in monocytes and validate in peripheral blood mononuclear cells a molecular signature of 25 genes that allows discrimination of the most severe forms of MIS-C with myocarditis., Multiparametric analysis identifies, in monocytes and dendritic cells, a molecular signature of the most severe forms of multisystem inflammatory syndrome in children caused by SARS-CoV-2 infection. Severe myocarditis is characterized by an excess of TNF-α signaling via NF-κB, hypoxic conditions, and hyperinflammation in the absence of type I and type II interferon responses.
Published: 2021
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30. Immune checkpoint inhibitors increase T cell immunity during SARS-CoV-2 infection

Author: Jeremy Boussier, Olivier Peyrony, Majdi Jebali, Bruno Charbit, Benjamin Terrier, Nora Kramkimel, Céleste Lebbé, Aurélien Corneau, Magnus Fontes, Jérôme LeGoff, Selim Aractingi, Laetitia Da Meda, Frédéric Rieux-Laucat, Vincent Calmettes, P. Tetu, Olivier Schwartz, Laura Barnabei, Darragh Duffy, Nikaïa Smith, Clara Allayous, Jérôme Hadjadj, Timothée Bruel, Charles Cassius, Nader Yatim, Isabelle Staropoli, F. Herms, Catherine Blanc, Ludivine Grzelak, Barouyr Baroudjian, Immunologie Translationnelle - Translational Immunology lab, Institut Pasteur [Paris]-Université Paris Cité (UPCité), Immunologie humaine, physiopathologie & immunothérapie (HIPI (UMR_S_976 / U976)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU), Virus et Immunité - Virus and immunity, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Cytometrie et Biomarqueurs – Cytometry and Biomarkers (UTechS CB), Immunogenetics of pediatric autoimmune diseases (Equipe Inserm U1163), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Cytométrie Pitié-Salpêtrière (PASS-CYPS), Unité Mixte de Service Production et Analyse de données en Sciences de la vie et en Santé (PASS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Université Paris Cité (UPCité), Hôpital Cochin [AP-HP], Laboratoire Roche [Boulogne-Billancourt], Vaccine Research Institute (VRI), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), N.Y. and C.L. acknowledge grant from the ARC Flash Covid-19 and Cancer call (ONCOVID). N.Y. and D.D. acknowledge grants from the Institut Pasteur for Covid-19 research and the ANR Flash Covid-19 call (CoVarImm). N.S. was supported by an Institut Pasteur Roux Cantarini fellowship. B.T. was supported by the Fonds IMMUNOV, for Innovation in Immunopathology. F.R.-L. acknowledges grants from the ANR Flash Covid-19 (AIROCOVID) and the FAST foundation. The study was also supported by the Institut National de la Santé et de la Recherche Médicale (Inserm) and by government grants managed by the Agence Nationale de la Recherche as part of the 'Investment for the future' program (ANR-10 IAHU-01 and ANR-18-RHUS-0010). L.B. was also supported by the EUR G.E.N.E. (reference #ANR-17-EURE-0013) and is part of the Université de Paris IdEx #ANR-18-IDEX-0001 funded by the French Government through its 'Investments for the future' program., ANR-20-COVI-0053,CoVarImm,Variation de la réponse immune systémique et muqueuse pendant l'infection par le SRAS-CoV-2 et la convalescence(2020), ANR-10-IAHU-0001,Imagine,Institut Hospitalo-Universitaire Imagine(2010), ANR-18-RHUS-0010,ATRACTION,Autoimmunity/inflammation Through Rnaseq Analysis at the single Cell level for Therapeutic Innovation(2018), ANR-17-EURE-0013,GENE,Génétique et Epigénétique Nouvelle Ecole(2017), ANR-18-IDEX-0001,Université de Paris,Université de Paris(2018), Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Vougny, Marie-Christine, Variation de la réponse immune systémique et muqueuse pendant l'infection par le SRAS-CoV-2 et la convalescence - - CoVarImm2020 - ANR-20-COVI-0053 - COVID-19 - VALID, Instituts Hospitalo-Universitaires - Institut Hospitalo-Universitaire Imagine - - Imagine2010 - ANR-10-IAHU-0001 - IAHU - VALID, Autoimmunity/inflammation Through Rnaseq Analysis at the single Cell level for Therapeutic Innovation - - ATRACTION2018 - ANR-18-RHUS-0010 - RHUS - VALID, Génétique et Epigénétique Nouvelle Ecole - - GENE2017 - ANR-17-EURE-0013 - EURE - VALID, Université de Paris - - Université de Paris2018 - ANR-18-IDEX-0001 - IDEX - VALID, Virus et Immunité - Virus and immunity (CNRS-UMR3569), Vaccine Research Institute [Créteil, France] (VRI), Institut Pasteur [Paris], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université de Paris (UP)
Subjects: Male, animal diseases, T-Lymphocytes, Adaptive Immunity, CD8-Positive T-Lymphocytes, Antibodies, Viral, Lymphocyte Activation, 0302 clinical medicine, Interferon, Prospective Studies, Immune Checkpoint Inhibitors, Melanoma, Research Articles, 0303 health sciences, Multidisciplinary, Effector, SciAdv r-articles, Middle Aged, Acquired immune system, 3. Good health, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Spike Glycoprotein, Coronavirus, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, medicine.symptom, medicine.drug, Research Article, [SDV.IMM] Life Sciences [q-bio]/Immunology, T cell, Immunology, Inflammation, chemical and pharmacologic phenomena, 03 medical and health sciences, Immune system, medicine, Humans, Health and Medicine, 030304 developmental biology, Aged, business.industry, SARS-CoV-2, COVID-19, biochemical phenomena, metabolism, and nutrition, medicine.disease, Coronavirus, bacteria, business, Immunologic Memory, CD8
Abstract: Immune checkpoint inhibitors for melanoma improve adaptive T cell immunity during COVID-19 without exacerbating inflammation., The COVID-19 pandemic has spread worldwide, yet the role of antiviral T cell immunity during infection and the contribution of immune checkpoints remain unclear. By prospectively following a cohort of 292 patients with melanoma, half of which treated with immune checkpoint inhibitors (ICIs), we identified 15 patients with acute or convalescent COVID-19 and investigated their transcriptomic, proteomic, and cellular profiles. We found that ICI treatment was not associated with severe COVID-19 and did not alter the induction of inflammatory and type I interferon responses. In-depth phenotyping demonstrated expansion of CD8 effector memory T cells, enhanced T cell activation, and impaired plasmablast induction in ICI-treated COVID-19 patients. The evaluation of specific adaptive immunity in convalescent patients showed higher spike (S), nucleoprotein (N), and membrane (M) antigen-specific T cell responses and similar induction of spike-specific antibody responses. Our findings provide evidence that ICI during COVID-19 enhanced T cell immunity without exacerbating inflammation.
Published: 2021
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31. Transmission of SARS-CoV-2 Alpha Variant (B.1.1.7) From a BNT162b2-Vaccinated Individual

Author: Timothée Bruel, Olivier Schwartz, Delphine Planas, Julien Puech, Hélène Péré, Sandrine Imbeaud, David Veyer, Solen Kernéis, Nicolas Robillard, Laurent Bélec, Thomas Vieillard, Julien Rodary, Isabelle Staropoli, AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Virus et Immunité - Virus and immunity, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Vaccine Research Institute (VRI), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Laboratoire Biosmose-idf [Rueil-Malmaison], Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Université Paris Cité - UFR Médecine [Santé] (UPCité UFR Médecine), Université Paris Cité (UPCité), D.P. is supported by the Vaccine Research Institute. D.V. and H.P. are funded by IDEX AAP EMERGENCE-Université de Paris (EMER-VEYER project) and Mécénat COVID APHP-CUP., Virus et Immunité - Virus and immunity (CNRS-UMR3569), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Vaccine Research Institute [Créteil, France] (VRI), École Pratique des Hautes Études (EPHE), UFR Médecine [Santé] - Université Paris Cité (UFR Médecine UPCité), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC)-Université Sorbonne Paris Nord, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC), Université Paris Cité - UFR Médecine [Santé] (UPC UFR Médecine), and Université Paris Cité (UPC)
Subjects: 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), Transmission (medicine), business.industry, SARS-CoV-2, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), viruses, transmission, Alpha (ethology), virus diseases, vaccination, Virology, Vaccination, Infectious Diseases, AcademicSubjects/MED00290, Oncology, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Medicine, Brief Reports, BNT162b2, Seroconversion, business
Abstract: Cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) acquisition after vaccination with BNT162b2 have been described, but the risk of secondary transmission from fully vaccinated individuals remains ill defined. Herein we report a confirmed transmission of SARS-CoV-2 alpha variant (B.1.1.7) from a symptomatic immunocompetent woman 4 weeks after her second dose of BNT162b2, despite antispike seroconversion.
Published: 2021
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32. SARS-CoV-2 infection induces the dedifferentiation of multiciliated cells and impairs mucociliary clearance

Author: Robinot, Rémy, Hubert, Mathieu, de Melo, Guilherme Dias, Lazarini, Françoise, Bruel, Timothée, Smith, Nikaïa, Levallois, Sylvain, Larrous, Florence, Fernandes, Julien, Gellenoncourt, Stacy, Rigaud, Stéphane, Gorgette, Olivier, Thouvenot, Catherine, Trébeau, Céline, Mallet, Adeline, Duménil, Guillaume, Gobaa, Samy, Etournay, Raphaël, Lledo, Pierre-Marie, Lecuit, Marc, Bourhy, Hervé, Duffy, Darragh, Michel, Vincent, Schwartz, Olivier, Chakrabarti, Lisa, Virus et Immunité - Virus and immunity, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Lyssavirus, épidémiologie et neuropathologie - Lyssavirus Epidemiology and Neuropathology, Institut Pasteur [Paris], Perception et Mémoire / Perception and Memory, Immunologie Translationnelle - Translational Immunology lab, Biologie des Infections - Biology of Infection, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), BioImagerie Photonique – Photonic BioImaging (UTechS PBI), Hub d'analyse d'images - Image Analysis Hub (Platform) (IAH), Institut de l'Audition [Paris] (IDA), Plateforme technologique Biomatériaux et Microfluidique - Biomaterials and Microfluidics technologic Platform, Service des Maladies infectieuses et tropicales [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Vaccine Research Institute (VRI), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), This work was supported by: Institut Pasteur TASK FORCE SARS COV2 (TROPICORO project), the Urgence COVID-19 Fundraising Campaign of Institut Pasteur (COROCHIP project), DIM ELICIT Region Ile-de-France, and Agence Nationale de Recherche sur le SIDA et les Maladies Infectieuses Emergentes (ANRS, project 19052) (L.A.C.), the Vaccine Research Institute (ANR-10-LABX-77), ANRS, Labex IBEID (ANR-10-LABX-62-IBEID), the French National Research Agency (ANR, projects 'TIMTAMDEN' ANR-14-CE14-0029, 'CHIKV-Viro-Immuno' ANR-14-CE14-0015-01), the Gilead HIV cure program, ANR/Fondation pour la Recherche Médicale (FRM) Flash Covid PROTEO-SARS-CoV-2 and IDISCOVR (O.S.), Institut Pasteur TASK FORCE SARS COV2 and ANR Flash Covid CoVarImm (D.D.), Institut Pasteur TASK FORCE SARS COV2 (Neuro-Covid project) (H.B.). The Lledo lab is supported by the life insurance company 'AG2R-La-Mondiale'. The UtechS Photonic BioImaging (Imagopole) and the UtechS Ultrastructural BioImaging (UBI) are supported by the ANR (France BioImaging, ANR-10–INSB–04, Investments for the Future). R.R. is the recipient of a Sidaction fellowship, N.S. of a Pasteur-Roux-Cantarini fellowship, and St.G. of a MESR/Ecole Doctorale B3MI, Université de Paris fellowship. S.L. is supported by FRM (fellowship ECO201906009119) and by 'Ecole Doctorale FIRE—Programme Bettencourt'., We thank Florence Guivel-Benhassine for help with virus titration, Charlotte Calvet for help with sample preparation for scanning electron microscopy, Sylvie Van der Werf for the SARS-CoV-2 isolate used in this study, and Nicolas Escriou for the gift of a SARS-CoV-2 spike antibody., ANR-10-LABX-0077,VRI,Initiative for the creation of a Vaccine Research Institute(2010), ANR-14-CE14-0029,TIMTAMDEN,Rôle des récepteurs TIM et TAM dans l'infection des cellules cibles par le virus de la dengue(2014), ANR-14-CE14-0015,CHIKV-Viro-Immuno,Multiplication et Relation avec l'hôte du virus Chikungunya(2014), Virus et Immunité - Virus and immunity (CNRS-UMR3569), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Vaccine Research Institute [Créteil, France] (VRI), Vougny, Marie-Christine, Laboratoires d'excellence - Initiative for the creation of a Vaccine Research Institute - - VRI2010 - ANR-10-LABX-0077 - LABX - VALID, Appel à projets générique - Rôle des récepteurs TIM et TAM dans l'infection des cellules cibles par le virus de la dengue - - TIMTAMDEN2014 - ANR-14-CE14-0029 - Appel à projets générique - VALID, and Appel à projets générique - Multiplication et Relation avec l'hôte du virus Chikungunya - - CHIKV-Viro-Immuno2014 - ANR-14-CE14-0015 - Appel à projets générique - VALID
Subjects: Male, Axoneme, [SDV.IMM] Life Sciences [q-bio]/Immunology, Science, viruses, MESH: Mesocricetus, MESH: Cricetinae, Respiratory Mucosa, MESH: Basal Bodies, Virus Replication, Article, MESH: Cilia, MESH: Forkhead Transcription Factors, Cricetinae, MESH: Respiratory Mucosa, Animals, Humans, MESH: COVID-19, MESH: Animals, MESH: SARS-CoV-2, MESH: Lung, Cilia, skin and connective tissue diseases, Lung, MESH: Cytokines, MESH: Humans, Mesocricetus, SARS-CoV-2, fungi, MESH: Virus Replication, COVID-19, Epithelial Cells, Forkhead Transcription Factors, respiratory system, MESH: Axoneme, Basal Bodies, MESH: Male, respiratory tract diseases, body regions, Mucociliary Clearance, MESH: Epithelial Cells, Cytokines, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH: Mucociliary Clearance
Abstract: Understanding how SARS-CoV-2 spreads within the respiratory tract is important to define the parameters controlling the severity of COVID-19. Here we examine the functional and structural consequences of SARS-CoV-2 infection in a reconstructed human bronchial epithelium model. SARS-CoV-2 replication causes a transient decrease in epithelial barrier function and disruption of tight junctions, though viral particle crossing remains limited. Rather, SARS-CoV-2 replication leads to a rapid loss of the ciliary layer, characterized at the ultrastructural level by axoneme loss and misorientation of remaining basal bodies. Downregulation of the master regulator of ciliogenesis Foxj1 occurs prior to extensive cilia loss, implicating this transcription factor in the dedifferentiation of ciliated cells. Motile cilia function is compromised by SARS-CoV-2 infection, as measured in a mucociliary clearance assay. Epithelial defense mechanisms, including basal cell mobilization and interferon-lambda induction, ramp up only after the initiation of cilia damage. Analysis of SARS-CoV-2 infection in Syrian hamsters further demonstrates the loss of motile cilia in vivo. This study identifies cilia damage as a pathogenic mechanism that could facilitate SARS-CoV-2 spread to the deeper lung parenchyma., SARS-CoV-2 infection damages the airways. Here the authors show that SARS-CoV-2 infection induces the rapid loss of airway motile cilia, resulting in altered cilia clearance function. Cilia loss is preceded by reduced expression of the ciliogenesis regulator Foxj1.
Published: 2021
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33. Analysis of T‐cell responses directed against the spike and/or membrane and/or nucleocapsid proteins in patients with chilblain‐like lesions during the COVID‐19 pandemic

Author: Assia Samri, Jean-David Bouaziz, P. Moghadam, Olivier Schwartz, Nader Yatim, D. Bergerat, C. Delaugerre, Martine Bagot, Jérôme LeGoff, C. Grolleau, Laure Frumholtz, Charles Cassius, L. Jaume, H. Le Buanec, Ludivine Grzelak, M. Merandet, Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Immunologie humaine, physiopathologie & immunothérapie (HIPI (UMR_S_976 / U976)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Centre d'Immunologie et des Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP), Virus et Immunité - Virus and immunity (CNRS-UMR3569), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Immunologie Translationnelle - Translational Immunology lab, Saint-Louis CORE (COvid REsearch), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Centre d'Immunologie et de Maladies Infectieuses (CIMI), Institut Pasteur [Paris], Virus et Immunité - Virus and immunity, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), and Le Buanec, Hélène
Subjects: 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), T-Lymphocytes, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), T cell, [SDV]Life Sciences [q-bio], Dermatology, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, Pandemic, Research Letter, medicine, Humans, Pandemics, Nucleocapsid Proteins, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, business.industry, COVID-19, Virology, 3. Good health, Chilblains, [SDV] Life Sciences [q-bio], medicine.anatomical_structure, Spike Glycoprotein, Coronavirus, Spike (software development), business
Abstract: International audience; No abstract available
Published: 2021
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34. A monocyte/dendritic cell molecular signature of SARS-CoV2-related multisystem inflammatory syndrome in children (MIS-C) with severe myocarditis

Author: Ludivine Grzelak, Maxime Beretta, Slimane Allali, Aude Magérus, Hugo Mouquet, Maxime Batignes, Isabelle Melki, Olivier Schwartz, Quentin Riller, Mehdi Oualha, Nicolas Cagnard, Christine Bole-Feysot, Camille de Cevins, James P. Di Santo, Christele Gras Leguen, Florence Moulin, Jean-Laurent Casanova, Cécile Masson, Aurélien Corneau, Damien Bonnet, Vithura Pirabarakan, Mickaël M. Ménager, Camille Bruneau, Brieuc P. Perot, Francesco Carbone, Darragh Duffy, Mohammed Zarhrate, Marie-Claude Stolzenberg, Alexandre Boullé, Mélanie Parisot, Boris Sorin, Ghaith Abdessalem, Alain Fischer, Marianne Leruez, Julie Toubiana, Victor Garcia-Paredes, Mathie Lorrot, Loïc de Pontual, Zahra Belhadjer, Bruno Charbit, Tinhinane Fali, Marine Luka, Nikaïa Smith, Brigitte Bader Meunier, Shen-Ying Zhang, Sonia Meynier, Fredéric Rieux Laucat, Julien Haroche, Pedro Gonçalves, Laura Barnabei, Inflammatory Responses and Transcriptomic Networks in diseases (Equipe Inserm U1163), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Sanofi Aventis R&D [Chilly-Mazarin], Immunologie Translationnelle - Translational Immunology lab, Institut Pasteur [Paris], Immunogenetics of pediatric autoimmune diseases (Equipe Inserm U1163), Cytometrie et Biomarqueurs – Cytometry and Biomarkers (UTechS CB), Immunologie humorale - Humoral Immunology, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Virus et Immunité - Virus and immunity, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Immunité Innée - Innate Immunity, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Structure Fédérative de Recherche Necker (SFR Necker - UMS 3633 / US24), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Cytométrie Pitié-Salpêtrière (PASS-CYPS), Unité Mixte de Service Production et Analyse de données en Sciences de la vie et en Santé (PASS), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Human genetics of infectious diseases : Mendelian predisposition (Equipe Inserm U1163), Rockefeller University [New York], Service d'immuno-hématologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Immunologie [CHU Pitié-Salpétrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), AP-HP Hôpital universitaire Robert-Debré [Paris], CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Département des urgences pédiatriques [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire de Virologie [CHU Necker], Département de Pédiatrie et maladies infectieuses [CHU Necker], Centre hospitalier universitaire de Nantes (CHU Nantes), Service de Pédiatrie [Jean Verdier], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Jean Verdier [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Sorbonne Paris Nord, Collège de France (CdF (institution)), Biodiversité et Epidémiologie des Bactéries pathogènes - Biodiversity and Epidemiology of Bacterial Pathogens, The study was supported by the Institut National de la Santé et de la Recherche Médicale (INSERM), by the 'URGENCE COVID-19' fundraising campaign of Institut Pasteur, by the Atip-Avenir, Emergence ville de Paris program and fond de dotation Janssen Horizon and by government grants managed by the Agence National de la Recherche as part of the 'Investment for the Future' program (Institut Hospitalo-Universitaire Imagine, grant ANR-10-IAHU-01, Recherche Hospitalo-Universitaire, grant ANR-18-RHUS-0010, Laboratoire d’Excellence ‘‘Milieu Intérieur', grant ANR-10-LABX-69-01), the Centre de Référence Déficits Immunitaires Héréditaires (CEREDIH), the Agence National de la Recherche (ANR-flash Covid19 'AIROCovid' to FRL and 'CoVarImm' to DD and JDS), and by the FAST Foundation (French Friends of Sheba Tel Hashomer Hospital). The LabTech Single Cell@Imagine is supported by the Paris Region and the 'Investissements d’avenir' program through the 2019 ATF funding – Sésame Filières PIA (Grant N°3877871). CdC is the recipient of a CIFRE-PhD (Sanofi). L.B. was a recipient of an Imagine institute PhD international program supported by the Fondation Bettencourt Schueller. L.B. was also supported by the EUR G.E.N.E. (reference #ANR-17-EURE-0013) and is part of the Université de Paris IdEx #ANR-18-IDEX-0001 funded by the French Government through its 'Investments for the Future' program. S.M. was a recipient of an INSERM and Institut Imagine post-doctorat program supported by the Fondation pour la Recherche Médicale (FRM N°SPF20170938825). NS was a recipient of the Pasteur-Roux-Cantarini Fellowship. VGP obtained an Imagine international PhD fellowship program supported by the Fondation Bettencourt Schueller. BPP is the recipient of an ANRS post-doctoral fellowship., ANR-10-IAHU-0001,Imagine,Institut Hospitalo-Universitaire Imagine(2010), ANR-18-RHUS-0010,ATRACTION,Autoimmunity/inflammation Through Rnaseq Analysis at the single Cell level for Therapeutic Innovation(2018), ANR-10-LABX-0069,MILIEU INTERIEUR,GENETIC & ENVIRONMENTAL CONTROL OF IMMUNE PHENOTYPE VARIANCE: ESTABLISHING A PATH TOWARDS PERSONALIZED MEDICINE(2010), ANR-20-COVI-0022,AIROCovid19,Analyse Omics de la réponse immune aigue au cours de l'infection à Covid19: rationnel moléculaire pour un traitement ciblé(2020), ANR-17-EURE-0013,GENE,Génétique et Epigénétique Nouvelle Ecole(2017), ANR-18-IDEX-0001,Université de Paris,Université de Paris(2018), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Institut Pasteur [Paris] (IP), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Virus et Immunité - Virus and immunity (CNRS-UMR3569), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)
Subjects: 0303 health sciences, Chemokine, Myocarditis, biology, business.industry, Monocyte, Dendritic cell, Gene signature, medicine.disease_cause, medicine.disease, Pathophysiology, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Immunology, biology.protein, medicine, [SDV.IMM]Life Sciences [q-bio]/Immunology, Tumor necrosis factor alpha, business, Oxidative stress, 030304 developmental biology
Abstract: SARS-CoV-2 infection in children is generally milder than in adults, yet a proportion of cases result in hyperinflammatory conditions often including myocarditis. To better understand these cases, we applied a multi-parametric approach to the study of blood cells of 56 children hospitalized with suspicion of SARS-CoV-2 infection. The most severe forms of MIS-C (multisystem inflammatory syndrome in children related to SARS-CoV-2), that resulted in myocarditis, were characterized by elevated levels of pro-angiogenesis cytokines and several chemokines. Single-cell transcriptomic analyses identified a unique monocyte/dendritic cell gene signature that correlated with the occurrence of severe myocarditis, characterized by sustained NF-κB activity, TNF-α signaling, associated with decreased gene expression of NF-κB inhibitors. We also found a weak response to type-I and type-II interferons, hyperinflammation and response to oxidative stress related to increased HIF-1α and VEGF signaling. These results provide potential for a better understanding of disease pathophysiology.
Published: 2021

35. Distinct systemic and mucosal immune responses to SARS-CoV-2

Author: Ludivine Grzelak, Bruno Charbit, Vincent Bondet, Hélène Péré, Hugo Mouquet, Cyril Planchais, Darragh Duffy, Benjamin Terrier, Vincent Rouilly, Sarah H. Merkling, Nader Yatim, Pedro Gonçalves, Maxime Beretta, Timothée Bruel, Frederic Rieux-Leucat, Nikaïa Smith, Solen Kernéis, Jérôme Hadjadj, James P. Di Santo, Olivier Schwartz, Immunologie Translationnelle - Translational Immunology lab, Institut Pasteur [Paris], Immunité Innée - Innate Immunity, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Cytometrie et Biomarqueurs – Cytometry and Biomarkers (UTechS CB), Virus et Immunité - Virus and immunity, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Université Sorbonne Paris Cité (USPC), Immunologie humorale - Humoral Immunology, Datactix, Immunogenetics of pediatric autoimmune diseases (Equipe Inserm U1163), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Department of Internal Medicine, National Referral Center for Rare Systemic Autoimmune Diseases, Assistance Publique Hôpitaux de Paris-Centre (APHP-CUP), Université de Paris, Paris, France, Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Interactions Virus-Insectes - Insect-Virus Interactions (IVI), Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Université Sorbonne Paris Nord, Epidémiologie et modélisation de la résistance aux antimicrobiens - Epidemiology and modelling of bacterial escape to antimicrobials (EMAE), This study was supported by an Institut Pasteur Covid-19 research grant and by a grant (CoVarImm) from the Agence National de la Recherche (ANR-flash Covid19) awarded to DD and JPD, and by the Laboratoire d’Excellence ‘‘Milieu Intérieur' (grant no. ANR-10-LABX-69-01) and the Fonds IMMUNOV, for Innovation in Immunopathology. NS is a recipient of the Pasteur-Roux-Cantarini Fellowship. We thank the UTechS CB of the Center for Translational Research, Institut Pasteur for supporting Luminex and Simoa analysis. We thank Laurence Motreff and Laurence Ma, Biomics Platform, C2RT, Institut Pasteur, Paris, France, supported by France Génomique (ANR-10-INBS-09-09), IBISA and the Illumina COVID-19 Projects’ offer for microbial sequencing., ANR-20-COVI-0053,CoVarImm,Variation de la réponse immune systémique et muqueuse pendant l'infection par le SRAS-CoV-2 et la convalescence(2020), ANR-10-LABX-0069,MILIEU INTERIEUR,GENETIC & ENVIRONMENTAL CONTROL OF IMMUNE PHENOTYPE VARIANCE: ESTABLISHING A PATH TOWARDS PERSONALIZED MEDICINE(2010), ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010), Institut Pasteur [Paris] (IP), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Virus et Immunité - Virus and immunity (CNRS-UMR3569), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord
Subjects: systemic immunity, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Proinflammatory cytokine, 03 medical and health sciences, 0302 clinical medicine, Immune system, Interferon, medicine, Microbiome, 030304 developmental biology, 0303 health sciences, biology, business.industry, Compartmentalization (psychology), cytokines, 3. Good health, Immunology, biology.protein, mucosal immunity, [SDV.IMM]Life Sciences [q-bio]/Immunology, Antibody, business, Covid-19, Viral load, 030217 neurology & neurosurgery, medicine.drug
Abstract: SummaryCoordinated local mucosal and systemic immune responses following SARS-CoV-2 infection protect against COVID-19 pathologies or fail leading to severe clinical outcomes. To understand this process, we performed an integrated analysis of SARS-CoV-2 spike-specific antibodies, cytokines, viral load and 16S bacterial communities in paired nasopharyngeal swabs and plasma samples from a cohort of clinically distinct COVID-19 patients during acute infection. Plasma viral load was associated with systemic inflammatory cytokines that were elevated in severe COVID-19, and also with spike-specific neutralizing antibodies. In contrast, nasopharyngeal viral load correlated with SARS-CoV-2 humoral responses but inversely with interferon responses, the latter associating with protective microbial communities. Potential pathogenic microrganisms, often implicated in secondary respiratory infections, were associated with mucosal inflammation and elevated in severe COVID-19. Our results demonstrate distinct tissue compartmentalization of SARS-CoV-2 immune responses and highlight a role for the nasopharyngeal microbiome in regulating local and systemic immunity that determines COVID-19 clinical outcomes.
Published: 2021

36. SARS-CoV-2 infection damages airway motile cilia and impairs mucociliary clearance

Author: Sylvain Levallois, Guillaume Duménil, Stéphane Rigaud, Françoise Lazarini, Olivier Gorgette, Lisa A. Chakrabarti, Rémy Robinot, Guilherme D. Melo, Julien Fernandes, Céline Trébeau, Pierre-Marie Lledo, Hervé Bourhy, Raphaël Etournay, Olivier Schwartz, Stacy Gellenoncourt, Samy Gobaa, Timothée Bruel, Florence Larrous, Mathieu Hubert, Marc Lecuit, Nikaïa Smith, Catherine Thouvenot, Darragh Duffy, Adeline Mallet, Vincent Michel, Virus et Immunité - Virus and immunity (CNRS-UMR3569), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Lyssavirus, épidémiologie et neuropathologie - Lyssavirus Epidemiology and Neuropathology, Institut Pasteur [Paris] (IP), Perception et Mémoire / Perception and Memory, Immunologie Translationnelle - Translational Immunology lab, Biologie des Infections - Biology of Infection, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), BioImagerie Photonique – Photonic BioImaging (UTechS PBI), Hub d'analyse d'images - Image Analysis Hub (Platform) (IAH), Plateforme BioImagerie Ultrastructurale – Ultrastructural BioImaging Platform (UTechS UBI), Institut de l'Audition [Paris] (IDA), Plateforme technologique Biomatériaux et Microfluidique - Biomaterials and Microfluidics technologic Platform, Institut National de la Santé et de la Recherche Médicale (INSERM), Vaccine Research Institute [Créteil, France] (VRI), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), This work was supported by : Institut Pasteur TASK FORCE SARS COV2 (Tropicoro project), DIM ELICIT Region Ile-de-France, and ANRS (L.A.C.), the Vaccine Research Institute (ANR-10-LABX-77), ANRS, Labex IBEID (ANR-10-LABX-62-IBEID), 'TIMTAMDEN' ANR-14-CE14-0029, 'CHIKV-Viro-Immuno' ANR-14-CE14- 0015-01, the Gilead HIV cure program, ANR/FRM Flash Covid PROTEO-SARS-CoV-2 and IDISCOVR (O.S.), Institut Pasteur TASK FORCE SARS COV2 and ANR Flash Covid CoVarImm (D.D.), Institut Pasteur TASK FORCE SARS COV2 (Neuro-Covid project) (H.B.). The Lledo’s lab is supported by the life insurance company 'AG2R-La-Mondiale'. The UtechS Photonic BioImaging (Imagopole) and the UtechS Ultrastructural BioImaging (UBI) are supported by the French National Research Agency (France BioImaging, ANR-10–INSB–04, Investments for the Future). R.R. is the recipient of a Sidaction fellowship, N.S. of a Pasteur-Roux Cantarini fellowship, and St.G. of a MESR/Ecole Doctorale B3MI, Paris 7 University fellowship. S.L. is supported by FRM (fellowship ECO201906009119) and by 'Ecole Doctorale FIRE – Programme Bettencourt'., ANR-10-LABX-0077,VRI,Initiative for the creation of a Vaccine Research Institute(2010), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-14-CE14-0029,TIMTAMDEN,Rôle des récepteurs TIM et TAM dans l'infection des cellules cibles par le virus de la dengue(2014), ANR-14-CE14-0015,CHIKV-Viro-Immuno,Multiplication et Relation avec l'hôte du virus Chikungunya(2014), ANR-20-COVI-0059,PROTEO-SARS-CoV-2,Protéomique du SARS-CoV-2(2020), ANR-20-COVI-0053,CoVarImm,Variation de la réponse immune systémique et muqueuse pendant l'infection par le SRAS-CoV-2 et la convalescence(2020), Virus et Immunité - Virus and immunity, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris], Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Vaccine Research Institute (VRI), and Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris]
Subjects: Axoneme, 0303 health sciences, Tight junction, Mucociliary clearance, Cilium, Biology, respiratory system, 3. Good health, Cell biology, respiratory tract diseases, 03 medical and health sciences, 0302 clinical medicine, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Parenchyma, Motile cilium, medicine, Basal body, [SDV.IMM]Life Sciences [q-bio]/Immunology, 030304 developmental biology, Respiratory tract
Abstract: Understanding how SARS-CoV-2 spreads within the respiratory tract is important to define the parameters controlling the severity of COVID-19. We examined the functional and structural consequences of SARS-CoV-2 infection in a reconstituted human bronchial epithelium model. SARS-CoV-2 replication caused a transient decrease in epithelial barrier function and disruption of tight junctions, though viral particle crossing remained limited. Rather, SARS-CoV-2 replication led to a rapid loss of the ciliary layer, characterized at the ultrastructural level by axoneme loss and misorientation of remaining basal bodies. The motile cilia function was compromised, as measured in a mucociliary clearance assay. Epithelial defense mechanisms, including basal cell mobilization and interferon-lambda induction, ramped up only after the initiation of cilia damage. Analysis of SARS-CoV-2 infection in Syrian hamsters further demonstrated the loss of motile ciliain vivo. This study identifies cilia damage as a pathogenic mechanism that could facilitate SARS-CoV-2 spread to the deeper lung parenchyma.
Published: 2021

37. SARS-CoV-2 infection in schools in a northern French city: a retrospective serological cohort study in an area of high transmission, France, January to April 2020

Author: Ludivine Grzelak, Charlotte Renaudat, Yoann Madec, Lucie Kuhmel, Laurence Arowas, Caroline Demeret, Kuang-Yu Chen, Christèle Huon, Marie Noelle Ungeheuer, Marc Eloit, Olivier Schwartz, Thomas Bigot, Bernadette Crescenzo-Chaigne, Sandrine Fernandes Pellerin, Arnaud Fontanet, Isabelle Staropoli, Bruno Hoen, Nathalie Jolly, Camille Besombes, Sandie Munier, Isabelle Cailleau, Timothée Bruel, Pierre Charneau, Laura Tondeur, Sarah Temmam, Blanca Liliana Perlaza, Rebecca Grant, Epidémiologie des Maladies Emergentes - Emerging Diseases Epidemiology, Pasteur-Cnam Risques infectieux et émergents (PACRI), Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM), Conservatoire National des Arts et Métiers [CNAM] (CNAM), Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM), Découverte de pathogènes – Pathogen discovery, Institut Pasteur [Paris], Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Virus et Immunité - Virus and immunity, Université de Paris (UP), Direction de la recherche médicale de l'Institut Pasteur, Investigation Clinique et d’Accès aux Ressources Biologiques (Plate-forme) - Clinical Investigation and Access to BioResources (ICAReB), Centre de Recherche Translationnelle - Center for Translational Science (CRT), Centre Médical de l'Institut Pasteur, Vaccine Research Institute (VRI), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Biologie des ARN et virus influenza - RNA Biology of Influenza Virus, Génétique Moléculaire des Virus à ARN - Molecular Genetics of RNA Viruses (GMV-ARN (UMR_3569 / U-Pasteur_2)), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Laboratoire commun Pasteur-TheraVectys, Institut Pasteur [Paris]-TheraVectys, Virologie Moléculaire et Vaccinologie / Molecular Virology and Vaccinology, École nationale vétérinaire d'Alfort (ENVA), The study was funded by Institut Pasteur, and several laboratories participating in the study receive funding from the Labex IBEID (ANR-10-LABX-62-IBEID), REACTing and the INCEPTION project (PIA/ANR-16-CONV-0005) for studies focusing on emerging viruses. OS lab is funded by Institut Pasteur, ANRS, Sidaction, the Vaccine Research Institute (ANR-10-LABX-77), 'TIMTAMDEN' ANR-14-CE14-0029, 'CHIKV-Viro- Immuno' ANR-14-CE14-0015-01 and the Gilead HIV cure program. LG is supported by the French Ministry of Higher Education, Research and Innovation. ME lab is funded by Institut Pasteur, Labex IBEID (ANR-10-LABX-62-IBEID), REACTing (Research & Action Emerging Infectious Diseases), EU Grant 101003589 RECoVER., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-16-CONV-0005,INCEPTION,Institut Convergences pour l'étude de l'Emergence des Pathologies au Travers des Individus et des populatiONs(2016), ANR-10-LABX-0077,VRI,Initiative for the creation of a Vaccine Research Institute(2010), ANR-14-CE14-0029,TIMTAMDEN,Rôle des récepteurs TIM et TAM dans l'infection des cellules cibles par le virus de la dengue(2014), ANR-14-CE14-0015,CHIKV-Viro-Immuno,Multiplication et Relation avec l'hôte du virus Chikungunya(2014), European Project: 101003589, H2020-SC1-PHE-CORONAVIRUS-2020,RECOVER(2020), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), Université Paris Cité (UPCité), Centre Médical de l'Institut Pasteur (CMIP), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), École nationale vétérinaire - Alfort (ENVA), Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris]-Université de Paris (UP), Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), Institut Pasteur [Paris] (IP), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Virus et Immunité - Virus and immunity (CNRS-UMR3569), Vaccine Research Institute [Créteil, France] (VRI), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), and Institut Pasteur [Paris] (IP)-TheraVectys
Subjects: 0301 basic medicine, Emerging infectious diseases, medicine.medical_specialty, MESH: Schools, Epidemiology, [SDV]Life Sciences [q-bio], Context (language use), Asymptomatic, Serology, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Virology, MESH: Child, Humans, Medicine, MESH: COVID-19, MESH: SARS-CoV-2, 030212 general & internal medicine, Child, MESH: Cohort Studies, Retrospective Studies, Schools, MESH: Humans, Transmission (medicine), business.industry, SARS-CoV-2, Research, 4. Education, Public Health, Environmental and Occupational Health, COVID-19, Outbreak, Retrospective cohort study, MESH: Retrospective Studies, 3. Good health, Coronavirus disease 2019 (COVID-19), MESH: France, 030104 developmental biology, France, medicine.symptom, business, Demography, Cohort study
Abstract: Background Children’s role in SARS-CoV-2 epidemiology remains unclear. We investigated an initially unnoticed SARS-CoV-2 outbreak linked to schools in northern France, beginning as early as mid-January 2020. Aims This retrospective observational study documents the extent of SARS-CoV-2 transmission, linked to an affected high school (n = 664 participants) and primary schools (n = 1,340 study participants), in the context of unsuspected SARS-CoV-2 circulation and limited control measures. Methods Between 30 March and 30 April 2020, all school staff, as well as pupils and their parents and relatives were invited for SARS-CoV-2 antibody testing and to complete a questionnaire covering symptom history since 13 January 2020. Results In the high school, infection attack rates were 38.1% (91/239), 43.4% (23/53), and 59.3% (16/27), in pupils, teachers, and non-teaching staff respectively vs 10.1% (23/228) and 12.0% (14/117) in the pupils’ parents and relatives (p Conclusions Viral circulation can occur in high and primary schools so keeping them open requires consideration of appropriate control measures and enhanced surveillance.
Published: 2021
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38. Sera neutralizing activities against SARS-CoV-2 and multiple variants six month after hospitalization for COVID-19

Author: Blandine Monel, David Veyer, Benoit Visseaux, Anne Blanchard, Antoine Fayol, David Lebeaux, Benoit Vedie, Maureen Betton, Hélène Péré, Jade Ghosn, Delphine Planas, Timothée Bruel, Marine Livrozet, Jean-Sébastien Hulot, Jean-Claude Manuguerra, Olivier Schwartz, Nicolas Robillard, Eric Tartour, Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), CIC - HEGP (CIC 1418), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Virus et Immunité - Virus and immunity, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Vaccine Research Institute (VRI), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service de biochimie [AP-HP Hôpital Européen Georges Pompidou], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Laboratoire d’immunologie [Hôpital Européen Georges Pompidou - APHP], Service de Microbiologie [CHU GeorgesPompidou], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Cellule d'Intervention Biologique d'Urgence (Centre National de Référence) - Laboratory for Urgent Response to Biological Threats (National Reference Center) (CIBU), Environnement et Risques infectieux - Environment and Infectious Risks (ERI), Institut Pasteur [Paris]-Institut Pasteur [Paris], Services de Maladies Infectieuses et Tropicales [CHU Bichat], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Université Sorbonne Paris Nord, Service de Virologie [CHU Bichat], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), The French COVID cohort is funding by the REACTing (REsearch & ACtion emergING infectious diseases) consortium and by a grant of the French Ministry of Health (PHRC n°20-0424). Work in OS lab is funded by Institut Pasteur, Urgence COVID-19 Fundraising Campaign of Institut Pasteur, Fondation pour la Recherche Médicale (FRM), ANRS, the Vaccine Research Institute (ANR-10-LABX-77), Labex IBEID (ANR-10-LABX-62-IBEID), ANR/FRM Flash Covid PROTEO-SARS-CoV-2 and IDISCOVR. Outside the submitted work, JSH is supported by AP-HP, INSERM, the French National Research Agency (NADHeart ANR-17-CE17-0015-02, PACIFIC ANR-18-CE14-0032-01, CORRECT_LMNA ANR-19-CE17-0013-02), the ERA-Net-CVD (ANR-16-ECVD-0011-03, Clarify project), Fédération Française de Cardiologie, the Fondation pour la Recherche Médicale, and by a grant from the Leducq Foundation (18CVD05), and is coordinating a French PIA Project (2018-PSPC-07, PACIFIC-preserved, BPIFrance) and a University Research Federation against heart failure (FHU2019, PREVENT_Heart Failure)., The French COVID cohort study group : Laurent ABEL (Inserm UMR 1163, Paris, France), Claire ANDREJAK (CHU Amiens, France), François ANGOULVANT (Hôpital Necker, Paris, France), Delphine BACHELET, Krishna BHAVSAR, Lila BOUADMA, Anissa CHAIR, Camille COUFFIGNAL, Charlene DA SILVEIRA, Marie-Pierre DEBRAY, Diane DESCAMPS, Xavier DUVAL, Philippine ELOY, Marina ESPOSITO-FARESE, Nadia ETTALHAOUI, Nathalie GAULT, Jade GHOSN, Isabelle GORENNE, Isabelle HOFFMANN, Ouifiya KAFIF, Sabrina KALI, Antoine KHALIL, Cédric LAOUÉNAN, Samira LARIBI, Minh LE, Quentin LE HINGRAT, François-Xavier LESCURE, Jean Christophe LUCET, France MENTRÉ, Jimmy Mullaert, Nathan PEIFFER-SMADJA, Gilles PEYTAVIN, Carine ROY, Marion SCHNEIDER, Nassima SI MOHAMMED, Lysa TAGHERSET, Coralie TARDIVON, Marie-Capucine TELLIER, Jean-François TIMSIT, Théo TRIOUX, Sarah TUBIANA, Benoit VISSEAUX, Yazdan YAZDANPANAH (Hôpital Bichat, Paris, France), Romain BASMACI, Olivier PICONE (Hôpital Louis Mourier, Colombes, France), Sylvie BEHILILL, Sylvie VAN DER WERF, Vincent ENOUF, Hugo MOUQUET (Pasteur Institute, Paris, France), Marine BELUZE (F-CRIN Partners Platform, Paris, France), Dehbia BENKERROU, Céline DORIVAL, François TÉOULÉ, Amina MEZIANE (Inserm UMR 1136, Paris, France), François BOMPART (Drugs for Neglected Diseases initiative, Geneva, Switzerland), Maude BOUSCAMBERT (Inserm UMR 1111, Lyon, France), Minerva CERVANTES-GONZALEZ, Eric d’ORTENZIO, Oriane PUÉCHAL, Caroline SEMAILLE (REACTing, Paris, France), Catherine CHIROUZE (CHRU Jean Minjoz, Besançon, France), Alexandra COELHO (Inserm UMR 1018, Paris, France), Sandrine COUFFIN-CADIERGUES, Hélène ESPEROU, Ikram HOUAS, Salma JAAFOURA, Aurélie PAPADOPOULOS (Inserm sponsor, Paris, France), Dominique DEPLANQUE (Hôpital Calmette, Lille, France), Mathilde DESVALLÉE, Coralie KHAN (Inserm UMR 1219, Bordeaux, France), Alpha DIALLO, Marie BARTOLI, Soizic LE MESTRE, Noémie MERCIER, Christelle PAUL, Ventzislava PETROV-SANCHEZ (ANRS, Paris, France), Alphonsine DIOUF, Alexandre HOCTIN, Marina MAMBERT (Inserm UMR 1018, Paris, France), François DUBOS (CHU Lille, France), Manuel ETIENNE (CHU Rouen, France), Alexandre GAYMARD (Inserm UMR 1111, Lyon, France), Tristan GIGANTE, Morgane GILG, Bénédicte ROSSIGNOL (F-CRIN INI-CRCT, Nancy, France), Jérémie GUEDJ, Hervé LE NAGARD, Guillaume LINGAS, Nadège NEANT (Inserm UMR 1137, Paris, France), Jean-Sébastien HULOT (Hôpital Européen Georges Pompidou, Paris, France), Florentia KAGUELIDOU, Justine PAGES (Hôpital Robert Debré, Paris, France), Yves LEVY, Aurélie WIEDEMANN (Vaccine Research Insitute (VRI), Inserm UMR 955, Créteil, France), Claire LEVY-MARCHAL (F-CRIN INI-CRCT, Paris, France), Bruno LINA, Manuel ROSA-CALATRAVA, Olivier TERRIER (Inserm UMR 1111, Lyon, France), Denis MALVY (CHU Bordeaux, France), Marion NORET (RENARCI, Annecy, France), Patrick ROSSIGNOL (CHU Nancy, France), Christelle TUAL, Aurélie VEISLINGER (Inserm CIC-1414, Rennes, France), Noémie VANEL (Hôpital la Timone, Marseille, France), ANR-10-LABX-0077,VRI,Initiative for the creation of a Vaccine Research Institute(2010), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-17-CE17-0015,NAD-HEART,Supplémentation en précurseur du NAD+ pour le traitement de l'insuffisance cardiaque(2017), ANR-18-CE14-0032,PACIFIC,Cellules PW1+ dans la fibrose cardiaque(2018), ANR-19-CE17-0013,Correct-LMNA,Édition génomique par CRISPR/Cas9 pour traiter les cardiomyopathies liées aux mutations du gène LMNA(2019), ANR-16-ECVD-0011,CLARIFY,Communication between cardiomyocytes and innate immune cells in failing hearts(2016), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Virus et Immunité - Virus and immunity (CNRS-UMR3569), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Vaccine Research Institute [Créteil, France] (VRI), Institut Pasteur [Paris] (IP)-Institut Pasteur [Paris] (IP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Agents infectieux, résistance et chimiothérapie - UR UPJV 4294 (AGIR ), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, CHU Amiens-Picardie, and French COVID cohort study group
Subjects: 0301 basic medicine, Microbiology (medical), [SDV]Life Sciences [q-bio], 030106 microbiology, Antibodies, Viral, medicine.disease_cause, Severity of Illness Index, Immunoglobulin G, Neutralization, law.invention, Serology, 03 medical and health sciences, 0302 clinical medicine, law, Intensive care, Major Article, Humans, Medicine, Prospective Studies, 030212 general & internal medicine, Prospective cohort study, Pandemics, Coronavirus, biology, SARS-CoV-2, business.industry, COVID-19, Antibodies, Neutralizing, Intensive care unit, 3. Good health, Hospitalization, Editorial Commentary, AcademicSubjects/MED00290, Infectious Diseases, Spike Glycoprotein, Coronavirus, Immunology, biology.protein, Antibody, business
Abstract: Background Humoral response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) occurs within the first weeks after coronavirus disease 2019 (COVID-19). Those antibodies exert a neutralizing activity against SARS-CoV-2, whose evolution over time after COVID-19 as well as efficiency against novel variants are poorly characterized. Methods In this prospective study, sera of 107 patients hospitalized with COVID-19 were collected at 3 and 6 months postinfection. We performed quantitative neutralization experiments on top of high-throughput serological assays evaluating anti-spike (S) and anti-nucleocapsid (NP) immunoglobulin G (IgG). Results Levels of seroneutralization and IgG rates against the ancestral strain decreased significantly over time. After 6 months, 2.8% of the patients had a negative serological status for both anti-S and anti-NP IgG. However, all sera had a persistent and effective neutralizing effect against SARS-CoV-2. IgG levels correlated with seroneutralization, and this correlation was stronger for anti-S than for anti-NP antibodies. The level of seroneutralization quantified at 6 months correlated with markers of initial severity, notably admission to intensive care units and the need for mechanical invasive ventilation. In addition, sera collected at 6 months were tested against multiple SARS-CoV-2 variants and showed efficient neutralizing effects against the D614G, B.1.1.7, and P.1 variants but significantly weaker activity against the B.1.351 variant. Conclusions Decrease in IgG rates and serological assays becoming negative did not imply loss of neutralizing capacity. Our results indicate a sustained humoral response against the ancestral strain and the D614G, B.1.1.7, and P.1 variants for at least 6 months in patients previously hospitalized for COVID-19. A weaker protection was, however, observed for the B.1.351 variant.
Published: 2021
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39. Sensitivity of infectious SARS-CoV-2 B.1.1.7 and B.1.351 variants to neutralizing antibodies

Author: Samira Fafi-Kremer, Maaran Michael Rajah, Julian Buchrieser, Flora Donati, Thierry Prazuck, Mélanie Albert, Hugo Mouquet, Florence Guivel-Benhassine, Sylvie van der Werf, Aymeric Sève, Etienne Simon-Loriere, Laurent Hocqueloux, Françoise Porrot, Emmanuelle Varon, Hélène Péré, Karl Stefic, Vincent Enouf, Frédérique Schortgen, Layla Yahyaoui, Olivier Schwartz, Sylvie Behillil, Marianne Maquart, David Veyer, María González, Delphine Planas, Jérôme De Seze, Isabelle Staropoli, Elodie Bishop, Timothée Bruel, Matthieu Prot, Mounira Smati-Lafarge, Ludivine Grzelak, Cyril Planchais, Virus et Immunité - Virus and immunity, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Vaccine Research Institute (VRI), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Université Paris Cité (UPCité), Immunologie humorale - Humoral Immunology, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Génétique Moléculaire des Virus à ARN - Molecular Genetics of RNA Viruses (GMV-ARN (UMR_3569 / U-Pasteur_2)), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Centre National de Référence des virus des infections respiratoires (dont la grippe) - National Reference Center Virus Influenzae [Paris] (CNR), Institut Pasteur [Paris], Génomique évolutive des virus à ARN - Evolutionary genomics of RNA viruses, Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Intercommunal de Créteil (CHIC), CHU Strasbourg, CIC Strasbourg (Centre d’Investigation Clinique Plurithématique (CIC - P) ), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Nouvel Hôpital Civil de Strasbourg-Hôpital de Hautepierre [Strasbourg], Génomique Fonctionnelle des Tumeurs Solides (U1162), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre Hospitalier Régional d'Orléans (CHRO), Université de Strasbourg (UNISTRA), Centre National de Référence du VIH [Tours] (CNR VIH), Work in the laboratory of O.S. is funded by Institut Pasteur, Urgence COVID-19 Fundraising Campaign of Institut Pasteur, ANRS, the Vaccine Research Institute (ANR-10-LABX-77), Labex IBEID (ANR-10-LABX-62-IBEID), ANR/FRM Flash COVID PROTEO-SARS-CoV-2 and IDISCOVR. Work in UPBI is funded by grant ANR-10-INSB-04-01 and Région Ile-de-France program DIM1-Health. D.P. is supported by the Vaccine Research Institute. L.G. is supported by the French Ministry of Higher Education, Research and Innovation. The laboratory of H.M. is funded by the Institut Pasteur, the Milieu Intérieur Program (ANR-10-LABX-69-01), the INSERM, REACTing and EU (RECOVER) grants. The laboratory of S.v.d.W. is funded by Institut Pasteur, CNRS, Université de Paris, Santé publique France, Labex IBEID (ANR-10-LABX-62-IBEID), REACTing, EU grant RECOVER. The laboratory of S.F.-K. is funded by Strasbourg University Hospital (SeroCoV-HUS, PRI 7782), Programme Hospitalier de Recherche Clinique (PHRC N 2017-HUS no. 6997), the Agence Nationale de la Recherche (ANR-18-CE17-0028), Laboratoire d’Excellence TRANSPLANTEX (ANR-11-LABX-0070_TRANSPLANTEX) and Institut National de la Santé et de la Recherche Médicale (UMR_S 1109). Work in CHR Orléans is funded by COREVIH Centre Val de Loire., ANR-10-LABX-0077,VRI,Initiative for the creation of a Vaccine Research Institute(2010), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-10-INBS-0004,France-BioImaging,Développment d'une infrastructure française distribuée coordonnée(2010), ANR-10-LABX-0069,MILIEU INTERIEUR,GENETIC & ENVIRONMENTAL CONTROL OF IMMUNE PHENOTYPE VARIANCE: ESTABLISHING A PATH TOWARDS PERSONALIZED MEDICINE(2010), ANR-18-CE17-0028,HuMABK,Les anticorps monoclonaux humains : une Nouvelle approche thérapeutique contre l'infection par le virus BK et les maladies associées(2018), ANR-11-LABX-0070,TRANSPLANTEX,Nouveaux loci d'histocompatibilité/biomarqueurs en transplantation humaine: de la découverte à l'app(2011), Université de Paris (UP), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Donati, Flora, Laboratoires d'excellence - Initiative for the creation of a Vaccine Research Institute - - VRI2010 - ANR-10-LABX-0077 - LABX - VALID, Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - VALID, Développment d'une infrastructure française distribuée coordonnée - - France-BioImaging2010 - ANR-10-INBS-0004 - INBS - VALID, Laboratoires d'excellence - GENETIC & ENVIRONMENTAL CONTROL OF IMMUNE PHENOTYPE VARIANCE: ESTABLISHING A PATH TOWARDS PERSONALIZED MEDICINE - - MILIEU INTERIEUR2010 - ANR-10-LABX-0069 - LABX - VALID, APPEL À PROJETS GÉNÉRIQUE 2018 - Les anticorps monoclonaux humains : une Nouvelle approche thérapeutique contre l'infection par le virus BK et les maladies associées - - HuMABK2018 - ANR-18-CE17-0028 - AAPG2018 - VALID, Nouveaux loci d'histocompatibilité/biomarqueurs en transplantation humaine: de la découverte à l'app - - TRANSPLANTEX2011 - ANR-11-LABX-0070 - LABX - VALID, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut Pasteur [Paris] (IP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Strasbourg (UNISTRA)-Hôpital de Hautepierre [Strasbourg]-Nouvel Hôpital Civil de Strasbourg, Virus et Immunité - Virus and immunity (CNRS-UMR3569), Vaccine Research Institute [Créteil, France] (VRI), Centre National de Référence des virus des infections respiratoires (dont la grippe) - National Reference Center Virus Influenzae [Paris] (CNR - laboratoire coordonnateur), and Centre National de Référence du VIH [Tours] - laboratoire associé (CNR VIH)
Subjects: 0301 basic medicine, COVID-19 Vaccines, media_common.quotation_subject, [SDV]Life Sciences [q-bio], Cross Reactions, Antibodies, Viral, Sensitivity and Specificity, General Biochemistry, Genetics and Molecular Biology, Neutralization, Virus, Flow cytometry, 03 medical and health sciences, 0302 clinical medicine, Immune system, Neutralization Tests, Humans, Medicine, media_common, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, biology, medicine.diagnostic_test, SARS-CoV-2, business.industry, Convalescence, Vaccination, COVID-19, General Medicine, Antibodies, Neutralizing, Virology, 3. Good health, [SDV] Life Sciences [q-bio], Titer, 030104 developmental biology, 030220 oncology & carcinogenesis, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, biology.protein, Antibody, business
Abstract: International audience; Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) B.1.1.7 and B.1.351 variants were first identified in the United Kingdom and South Africa, respectively, and have since spread to many countries. These variants harboring diverse mutations in the gene encoding the spike protein raise important concerns about their immune evasion potential. Here, we isolated infectious B.1.1.7 and B.1.351 strains from acutely infected individuals. We examined sensitivity of the two variants to SARS-CoV-2 antibodies present in sera and nasal swabs from individuals infected with previously circulating strains or who were recently vaccinated, in comparison with a D614G reference virus. We utilized a new rapid neutralization assay, based on reporter cells that become positive for GFP after overnight infection. Sera from 58 convalescent individuals collected up to 9 months after symptoms, similarly neutralized B.1.1.7 and D614G. In contrast, after 9 months, convalescent sera had a mean sixfold reduction in neutralizing titers, and 40% of the samples lacked any activity against B.1.351. Sera from 19 individuals vaccinated twice with Pfizer Cominarty, longitudinally tested up to 6 weeks after vaccination, were similarly potent against B.1.1.7 but less efficacious against B.1.351, when compared to D614G. Neutralizing titers increased after the second vaccine dose, but remained 14-fold lower against B.1.351. In contrast, sera from convalescent or vaccinated individuals similarly bound the three spike proteins in a flow cytometry-based serological assay. Neutralizing antibodies were rarely detected in nasal swabs from vaccinees. Thus, faster-spreading SARS-CoV-2 variants acquired a partial resistance to neutralizing antibodies generated by natural infection or vaccination, which was most frequently detected in individuals with low antibody levels. Our results indicate that B1.351, but not B.1.1.7, may increase the risk of infection in immunized individuals.
Published: 2021
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40. Quantitative characterization of extracellular vesicle uptake and content delivery within mammalian cells

Author: Bonsergent, Emeline, Grisard, Eleonora, Buchrieser, Julian, Schwartz, Olivier, Théry, Clotilde, Lavieu, Grégory, Immunité et cancer (U932), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Matière et Systèmes Complexes (MSC (UMR_7057)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPC), Virus et Immunité - Virus and immunity, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), E.B. is a recipient of a PhD fellowship from La ligue contre le Cancer. E.G. is a recipient of a post-doctoral fellowship from Fondation pour la Recherche Médicale (FRM (FRM: SPF20170938694). This work is supported by Fondation ARC (PJA20171206453 and PGA1 RF20180206962), Cancéropôle Île‐de‐France (Emergence 2018) and French National Research Agency (ANR‐10‐IDEX‐0001‐02 PSL*, ANR‐11‐LABX‐0043, and ANR‐18‐CE15‐0008, ANR-19-CE18-002003), and ANR-18-IDEX-0001, IdEx Université de Paris. OS lab is funded by Institut Pasteur, ANRS, Sidaction, the Vaccine Research Institute (ANR-10-LABX-77), Labex IBEID (ANR-10-LABX-62-IBEID), 'TIMTAMDEN' ANR-14-CE14-0029, 'CHIKV-Viro-Immuno' ANR-14-CE14-0015-01, ANR/FRM Covid support, and the Gilead HIV cure program., We thank Mathieu Maurin for his input on image quantification. We thank Nicolas Manel for his suggestion concerning the IFITMs. We thank Alena Ivanova and Michael Boutros for introducing us to NanoLuc Luciferase. We thank Marine Gros for her help with Galectin3-related experiments., ANR-10-IDEX-0001,PSL,Paris Sciences et Lettres(2010), ANR-11-LABX-0043,DCBIOL,Biologie des cellules dendritiques(2011), ANR-18-CE15-0008,EVUp,Mécanismes moléculaires et cellulaires du transfert d'antigènes aux cellules dendritiques par les vésicules extracellulaires(2018), ANR-19-CE18-0020,EXCELLDISC,Vésicules Extracellulaires et thérapie du disque intervertébral(2019), ANR-18-IDEX-0001,Université de Paris,Université de Paris(2018), ANR-10-LABX-0077,VRI,Initiative for the creation of a Vaccine Research Institute(2010), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-14-CE14-0029,TIMTAMDEN,Rôle des récepteurs TIM et TAM dans l'infection des cellules cibles par le virus de la dengue(2014), ANR-14-CE14-0015,CHIKV-Viro-Immuno,Multiplication et Relation avec l'hôte du virus Chikungunya(2014), Matière et Systèmes Complexes (MSC), Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Virus et Immunité - Virus and immunity (CNRS-UMR3569), and Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Cell biology, Science, Biological Transport, Membrane trafficking, Cell Communication, Antigens, Differentiation, Membrane Fusion, Article, Extracellular Vesicles, Cytosol, HEK293 Cells, Cell Line, Tumor, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Humans, Macrolides, Enzyme Inhibitors, Luciferases, Fluorescent Dyes, HeLa Cells
Abstract: Extracellular vesicles (EVs), including exosomes, are thought to mediate intercellular communication through the transfer of cargoes from donor to acceptor cells. Occurrence of EV-content delivery within acceptor cells has not been unambiguously demonstrated, let alone quantified, and remains debated. Here, we developed a cell-based assay in which EVs containing luciferase- or fluorescent-protein tagged cytosolic cargoes are loaded on unlabeled acceptor cells. Results from dose-responses, kinetics, and temperature-block experiments suggest that EV uptake is a low yield process (~1% spontaneous rate at 1 h). Further characterization of this limited EV uptake, through fractionation of membranes and cytosol, revealed cytosolic release (~30% of the uptaken EVs) in acceptor cells. This release is inhibited by bafilomycin A1 and overexpression of IFITM proteins, which prevent virus entry and fusion. Our results show that EV content release requires endosomal acidification and suggest the involvement of membrane fusion., Extracellular vesicles mediate cell–cell communication, however, their capacity to deliver their content within acceptor cells is unclear. Here, the authors develop a quantitative assay and show that release of extracellular vesicle contents requires endosomal acidification and may involve membrane fusion.
Published: 2021
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41. Distinct systemic and mucosal immune responses during acute SARS-CoV-2 infection

Author: Smith, Nikaïa, Goncalves, Pedro, Charbit, Bruno, Grzelak, Ludivine, Beretta, Maxime, Planchais, Cyril, Bruel, Timothée, Rouilly, Vincent, Bondet, Vincent, Hadjadj, Jérôme, Yatim, Nader, Pere, Helene, Merkling, Sarah H., Ghozlane, Amine, Kernéis, Solen, Rieux-Laucat, Frederic, Terrier, Benjamin, Schwartz, Olivier, Mouquet, Hugo, Duffy, Darragh, Di Santo, James P., Immunologie Translationnelle - Translational Immunology lab, Institut Pasteur [Paris], Immunité Innée - Innate Immunity, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Cytometrie et Biomarqueurs – Cytometry and Biomarkers (UTechS CB), Virus et Immunité - Virus and immunity, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Université de Paris (UP), Immunologie humorale - Humoral Immunology, Datactix, Service de médecine interne et centre de référence des maladies rares [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Immunogenetics of pediatric autoimmune diseases (Equipe Inserm U1163), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), Interactions Virus-Insectes - Insect-Virus Interactions (IVI), Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Hôpital Cochin [AP-HP], Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Université Sorbonne Paris Nord, Epidémiologie et modélisation de la résistance aux antimicrobiens - Epidemiology and modelling of bacterial escape to antimicrobials (EMAE), This study was supported by grants from the Institut Pasteur (CoVarImm) and from the Agence National de la Recherche (ANR-flash COVID-19, to D.D. and J.P.D.), and by the Laboratoire d’Excellence ‘Milieu Intérieur’ (grant no. ANR-10-LABX-69-01) and the Fonds IMMUNOV, for Innovation in Immunopathology. N.S. is a recipient of the Pasteur-Roux-Cantarini Fellowship., We thank the UTechS CB of the Center for Translational Research, Institut Pasteur for supporting Luminex and Simoa analysis. We thank L. Motreff and L. Ma (Biomics Platform supported by France Génomique, ANR-10-INBS-09-09), IBISA and the Illumina COVID-19 Projects’ offer for microbial sequencing. We thank the Bioinformatics and Biostatistics HUB, Institut Pasteur for the assistance with the 16S rRNA-sequencing data analysis. We acknowledge all health-care workers involved in the diagnosis and treatment of patients in Cochin Hospital, especially C. Azoulay, L. Beaudeau, E. Canoui, P. Cohen, A. Contejean, B. Dunogué, D. Journois, P. Legendre, J. Marey and A. Régent., ANR-20-COVI-0053,CoVarImm,Variation de la réponse immune systémique et muqueuse pendant l'infection par le SRAS-CoV-2 et la convalescence(2020), ANR-10-LABX-0069,MILIEU INTERIEUR,GENETIC & ENVIRONMENTAL CONTROL OF IMMUNE PHENOTYPE VARIANCE: ESTABLISHING A PATH TOWARDS PERSONALIZED MEDICINE(2010), BONDET, Vincent, Variation de la réponse immune systémique et muqueuse pendant l'infection par le SRAS-CoV-2 et la convalescence - - CoVarImm2020 - ANR-20-COVI-0053 - COVID-19 - VALID, Laboratoires d'excellence - GENETIC & ENVIRONMENTAL CONTROL OF IMMUNE PHENOTYPE VARIANCE: ESTABLISHING A PATH TOWARDS PERSONALIZED MEDICINE - - MILIEU INTERIEUR2010 - ANR-10-LABX-0069 - LABX - VALID, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Université Paris Cité (UPCité), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Virus et Immunité - Virus and immunity (CNRS-UMR3569), and École Pratique des Hautes Études (EPHE)
Subjects: Adult, Male, Adolescent, viruses, [SDV]Life Sciences [q-bio], Adaptive immunity, Antibodies, Viral, Article, Cohort Studies, Young Adult, Nasopharynx, Humans, Immunity, Mucosal, Aged, Bacteria, SARS-CoV-2, Microbiota, COVID-19, Middle Aged, Viral Load, Gastrointestinal Microbiome, Immunity, Humoral, [SDV] Life Sciences [q-bio], Viral infection, Acute Disease, Spike Glycoprotein, Coronavirus, Cytokines, Mucosal immunology, Female, Interferons
Abstract: Coordinated local mucosal and systemic immune responses following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection either protect against coronavirus disease 2019 (COVID-19) pathologies or fail, leading to severe clinical outcomes. To understand this process, we performed an integrated analysis of SARS-CoV-2 spike-specific antibodies, cytokines, viral load and bacterial communities in paired nasopharyngeal swabs and plasma samples from a cohort of clinically distinct patients with COVID-19 during acute infection. Plasma viral load was associated with systemic inflammatory cytokines that were elevated in severe COVID-19, and also with spike-specific neutralizing antibodies. By contrast, nasopharyngeal viral load correlated with SARS-CoV-2 humoral responses but inversely with interferon responses, the latter associating with protective microbial communities. Potential pathogenic microorganisms, often implicated in secondary respiratory infections, were associated with mucosal inflammation and elevated in severe COVID-19. Our results demonstrate distinct tissue compartmentalization of SARS-CoV-2 immune responses and highlight a role for the nasopharyngeal microbiome in regulating local and systemic immunity that determines COVID-19 clinical outcomes., Mucosal surfaces of the respiratory tract are the first sites of entry and defense against SARS-CoV-2. Di Santo and colleagues perform paired analysis of the nasopharyngeal and systemic immune responses of SARS-CoV-2-infected patients and demonstrate distinct compartmentalization of immunity and shifts in the microbiome.
Published: 2021
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42. Serological reconstruction of COVID-19 epidemics through analysis of antibody kinetics to SARS-CoV-2 proteins

Author: Thomas Obadia, Solen Kernéis, Konstantinos Zannis, Cliona Ni Cheallaigh, Laura Garcia, María Victoria González, Tom Woudenberg, Samira Fafi-Kremer, Stéphane Petres, Jérôme De Seze, Benjamin Terrier, François Dejardin, Delphine Planas, Marija Backovic, Ivo Mueller, Françoise Donnadieu, Laurence Arowas, Charlotte Cockram, Aurélie Velay, Darragh Duffy, Bruno Hoen, Nizar Khelil, Louise Perrin de Facci, Sarah H. Merkling, Timothée Bruel, Heidi Auerswald, Annalisa Meola, Arnaud Fontanet, Jacques Yves Nizou, Niall Conlon, Cassandre Von Platen, Soazic Gardais, Yasmine Elgharbawy, Olivier Schwartz, Michael A. White, Liam Townsend, Jason Rosado, Stéphane Pelleau, Malaria : parasites et hôtes - Malaria : parasites and hosts, Institut Pasteur [Paris] (IP), Laboratoire de Virologie [Strasbourg], Institut Mutualiste de Montsouris (IMM), Département de Génomes et Génétique - Department of Genomes and Genetics, Interactions Virus-Insectes - Insect-Virus Interactions (IVI), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Virologie Structurale - Structural Virology, GHU AP-HP Centre Université de Paris, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CIC Strasbourg (Centre d’Investigation Clinique Plurithématique (CIC - P) ), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Nouvel Hôpital Civil de Strasbourg-Hôpital de Hautepierre [Strasbourg], Virus et Immunité - Virus and immunity (CNRS-UMR3569), Plateforme technologique Production et purification de protéines recombinantes – Production and Purification of Recombinant Proteins Technological Platform (PPR), Centre de Recherche Translationnelle - Center for Translational Science (CRT), Investigation Clinique et d’Accès aux Ressources Biologiques (Plate-forme) - Clinical Investigation and Access to BioResources (ICAReB), Immunologie Translationnelle - Translational Immunology lab, St James's University Hospital, Leeds Teaching Hospitals NHS Trust, Trinity College Dublin, Unité de Virologie / Virology Unit [Phnom Penh], Institut Pasteur du Cambodge, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Direction de la recherche médicale de l'Institut Pasteur, Epidémiologie des Maladies Emergentes - Emerging Diseases Epidemiology, Pasteur-Cnam Risques infectieux et émergents (PACRI), Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), Michael, White, Institut Pasteur [Paris], Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Centre National de Référence Maladies auto-immunes Systémiques Rares [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Strasbourg (UNISTRA)-Hôpital de Hautepierre [Strasbourg]-Nouvel Hôpital Civil de Strasbourg, Virus et Immunité - Virus and immunity, Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM), Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM), Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: 0303 health sciences, biology, Transmission (medicine), business.industry, [SDV]Life Sciences [q-bio], Isotype, Confidence interval, Orders of magnitude (mass), 3. Good health, Serology, [SDV] Life Sciences [q-bio], 03 medical and health sciences, 0302 clinical medicine, Antigen, Immunology, biology.protein, Medicine, Multiplex, 030212 general & internal medicine, Antibody, business, 030304 developmental biology
Abstract: Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces a complex antibody response that varies by orders of magnitude between individuals and over time. Waning antibody levels lead to reduced sensitivity of serological diagnostic tests over time. This undermines the utility of serological surveillance as the SARS-CoV-2 pandemic progresses into its second year. Here we develop a multiplex serological test for measuring antibodies of three isotypes (IgG, IgM, IgA) to five SARS-CoV-2 antigens (Spike (S), receptor binding domain (RBD), Nucleocapsid (N), Spike subunit 2, Membrane-Envelope fusion) and the Spike proteins of four seasonal coronaviruses. We measure antibody responses in several cohorts of French and Irish hospitalized patients and healthcare workers followed for up to eleven months after symptom onset. The data are analysed with a mathematical model of antibody kinetics to quantify the duration of antibody responses accounting for inter-individual variation. One year after symptoms, we estimate that 36% (95% range: 11%, 94%) of anti-S IgG remains, 31% (9%, 89%) anti-RBD IgG remains, and 7% (1%, 31%) anti-N IgG remains. Antibodies of the IgM isotype waned more rapidly, with 9% (2%, 32%) anti-RBD IgM remaining after one year. Antibodies of the IgA isotype also waned rapidly, with 10% (3%, 38%) anti-RBD IgA remaining after one year. Quantitative measurements of antibody responses were used to train machine learning algorithms for classification of previous infection and estimation of time since infection. The resulting diagnostic test classified previous infections with 99% specificity and 98% (95% confidence interval: 94%, 99%) sensitivity, with no evidence for declining sensitivity over the time scale considered. The diagnostic test also provided accurate classification of time since infection into intervals of 0 – 3 months, 3 – 6 months, and 6 – 12 months. Finally, we present a computational method for serological reconstruction of past SARS-CoV-2 transmission using the data from this test when applied to samples from a single cross-sectional sero-prevalence survey.
Published: 2021

43. Cluster of COVID-19 in northern France: A retrospective closed cohort study

Author: Nathalie Jolly, Christèle Huon, Laura Tondeur, Bernadette Crescenzo, Sarah Temmam, Sandie Munier, Camille Besombes, Isabelle Staropoli, Timothée Bruel, Isabelle Cailleau, Rebecca Grant, Pierre Gallian, Simon Cauchemez, Marie-Noëlle Ungeheuer, Yoann Madec, Sylvie van der Werf, Bruno Hoen, Ludivine Grzelak, Marc Eloit, Sandrine Fernandes Pellerin, Olivier Schwartz, Caroline Demeret, Kuang-Yu Chen, Arnaud Fontanet, Lucie Kuhmel, Epidémiologie des Maladies Emergentes - Emerging Diseases Epidemiology, Pasteur-Cnam Risques infectieux et émergents (PACRI), Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), Sorbonne Université (SU), Centre de Recherche Translationnelle - Center for Translational Science (CRT), Institut Pasteur [Paris] (IP), Investigation Clinique et d’Accès aux Ressources Biologiques (Plate-forme) - Clinical Investigation and Access to BioResources (ICAReB), Direction de la recherche médicale de l'Institut Pasteur, Centre Médical de l'Institut Pasteur (CMIP), Découverte de pathogènes – Pathogen discovery, Biologie des ARN et virus influenza - RNA Biology of Influenza Virus, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Génétique Moléculaire des Virus à ARN - Molecular Genetics of RNA Viruses (GMV-ARN (UMR_3569 / U-Pasteur_2)), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Virus et Immunité - Virus and immunity (CNRS-UMR3569), Université Paris Cité (UPCité), Etablissement Français du Sang [La Plaine Saint-Denis] (EFS), Unité des Virus Emergents (UVE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Modélisation mathématique des maladies infectieuses - Mathematical modelling of Infectious Diseases, École nationale vétérinaire - Alfort (ENVA), Funding: Institut Pasteur, CNRS, Université de Paris, Santé publique France, Labex IBEID (ANR-10-LABX-62-IBEID), REACTing, EU grant Recover, INCEPTION project (PIA/ANR-16-CONV-0005)., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-16-CONV-0005,INCEPTION,Institut Convergences pour l'étude de l'Emergence des Pathologies au Travers des Individus et des populatiONs(2016), European Project: 101003589, H2020-SC1-PHE-CORONAVIRUS-2020,RECOVER(2020), Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM), Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM), Institut Pasteur [Paris], Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris]-Université de Paris (UP), Virus et Immunité - Virus and immunity, Université de Paris (UP), École nationale vétérinaire d'Alfort (ENVA), demeret, caroline, Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - VALID, Institut Convergences pour l'étude de l'Emergence des Pathologies au Travers des Individus et des populatiONs - - INCEPTION2016 - ANR-16-CONV-0005 - CONV - VALID, Rapid European COVID-19 Emergency Response research - RECOVER - - H2020-SC1-PHE-CORONAVIRUS-20202020-02-14 - 2022-02-13 - 101003589 - VALID, Centre Médical de l'Institut Pasteur, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), and Aix Marseille Université (AMU)-Institut de Recherche pour le Développement (IRD)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: 0303 health sciences, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), business.industry, [SDV]Life Sciences [q-bio], Attack rate, Ageusia, Disease cluster, Confidence interval, 3. Good health, Herd immunity, [SDV] Life Sciences [q-bio], 03 medical and health sciences, 0302 clinical medicine, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Internal medicine, Case fatality rate, medicine, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, 030212 general & internal medicine, medicine.symptom, business, 030304 developmental biology, Cohort study
Abstract: SummaryBackgroundThe Oise department in France has been heavily affected by COVID-19 in early 2020.MethodsBetween 30 March and 4 April 2020, we conducted a retrospective closed cohort study among pupils, their parents and siblings, as well as teachers and non-teaching staff of a high-school located in Oise. Participants completed a questionnaire that covered history of fever and/or respiratory symptoms since 13 January 2020 and had blood tested for the presence of anti-SARS-CoV-2 antibodies. The infection attack rate (IAR) was defined as the proportion of participants with confirmed SARS-CoV-2 infection based on antibody detection. Blood samples from two blood donor centres collected between 23 and 27 March 2020 in the Oise department were also tested for presence of anti-SARS-CoV-2 antibodies.FindingsOf the 661 participants (median age: 37 years), 171 participants had anti-SARS-CoV-2 antibodies. The overall IAR was 25.9% (95% confidence interval (CI) = 22.6-29.4), and the infection fatality rate was 0% (one-sided 97.5% CI = 0 - 2.1). Nine of the ten participants hospitalised since mid-January were in the infected group, giving a hospitalisation rate of 5.3% (95% CI = 2.4 –9.8). Anosmia and ageusia had high positive predictive values for SARS-CoV-2 infection (84.7% and 88.1%, respectively). Smokers had a lower IAR compared to non-smokers (7.2% versus 28.0%, P InterpretationThe relatively low IAR observed in an area where SARS-CoV-2 actively circulated weeks before confinement measures indicates that establishing herd immunity will take time, and that lifting these measures in France will be long and complex.FundingInstitut Pasteur, CNRS, Université de Paris, Santé publique France, Labex IBEID (ANR-10-LABX-62-IBEID), REACTing, EU grant Recover, INCEPTION project (PIA/ANR-16-CONV-0005).Research in contextEvidence before the studyThe first COVID-19 cases in France were reported on 24 January 2020. Substantial transmission has occurred since then, with the Oise department, north of Paris, one of the heaviest affected areas in the early stages of the epidemic in France. As of 13 April 2020, 98,076 cases had been diagnosed in France, including 5,379 deaths.Epidemiological and clinical characteristics of patients with COVID-19 have been widely reported, but this has largely been centred on cases requiring medical care. What remains unclear at this stage is the extent to which SARS-CoV-2 infections may be asymptomatic or present as subclinical, non-specific symptoms. While extensive contact tracing has identified asymptomatic infections using RT-PCR testing, serologic detection of anti-SARS-CoV-2 antibodies is needed to determine the real infection attack rate and the proportion of all infections that are asymptomatic or subclinical.Added value of this studyUsing a combination of serologic assays with high sensitivity and specificity for anti-SARS-CoV-2 antibodies, we conducted a retrospective closed cohort study. In a high school linked to a cluster of COVID-19 in the Oise department, we showed an overall infection attack rate (IAR) of 40.9% in the high school group, and 10.9% in parents and siblings of the pupils. The proportion of infected individuals who had no symptoms during the study period was 17.0%.Implications of all of the available evidenceThe relatively low IAR in this area where SARS-CoV-2 actively circulated before confinement measures were introduced indicates that establishing herd immunity will take time, and that the lifting of these measures in France will be long and complex.
Published: 2021

44. Evolution of antibody responses up to 13 months after SARS-CoV-2 infection and risk of reinfection

Author: Anne Schneider, Aurélie Velay, David Rey, Arnaud Fontanet, Timothée Bruel, Baptiste Panaget, Nicolas Meyer, Yves Hansmann, Laurence Kling-Pillitteri, Olivier Schwartz, Floriane Gallais, Samira Fafi-Kremer, Elodie Laugel, Pierre Gantner, María González, Nathalie Reix, Catherine Schmidt-Mutter, Jean-Marc Lessinger, Jérôme De Seze, Ludovic Glady, Marialuisa Partisani, Nicolas Collongues, Morgane Solis, Marie-Josée Wendling, Sophie Bayer, Delphine Planas, Bertram, Marie-Liesse, APPEL À PROJETS GÉNÉRIQUE 2018 - Les anticorps monoclonaux humains : une Nouvelle approche thérapeutique contre l'infection par le virus BK et les maladies associées - - HuMABK2018 - ANR-18-CE17-0028 - AAPG2018 - VALID, Nouveaux loci d'histocompatibilité/biomarqueurs en transplantation humaine: de la découverte à l'app - - TRANSPLANTEX2011 - ANR-11-LABX-0070 - LABX - VALID, Laboratoire de Virologie [Strasbourg], Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Virus et Immunité - Virus and immunity, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Vaccine Research Institute (VRI), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Les Hôptaux universitaires de Strasbourg (HUS), CHU Strasbourg, Laboratoire de Génétique Moléculaire [CHRU Strasbourg], CHRU Strasbourg, CIC Strasbourg (Centre d’Investigation Clinique Plurithématique (CIC - P) ), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Nouvel Hôpital Civil de Strasbourg-Hôpital de Hautepierre [Strasbourg], Le Trait d'Union, centre de soins de l'infection par le VIH [CHU Strasbourg], Epidémiologie des Maladies Emergentes - Emerging Diseases Epidemiology, Université Paris Cité (UPCité)-Pasteur-Cnam Risques infectieux et émergents (PACRI), Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Paris Cité (UPCité)-Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), Pasteur-Cnam Risques infectieux et émergents (PACRI), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Paris Cité (UPCité), Service des Maladies Infectieuses et Tropicales [CHU Strasbourg], Service de Santé Publique [Strasbourg] (HUS), Les Hôpitaux Universitaires de Strasbourg (HUS), This work was supported by Strasbourg University Hospital (SeroCoV-HUS, PRI 7782), the Agence Nationale de la Recherche (ANR-18-CE17-0028), Laboratoire d'Excellence TRANSPLANTEX (ANR-11-LABX-0070_TRANSPLANTEX), Strasbourg University and Institut National de la Santé et de la Recherche Médicale (UMR_S 1109)., ANR-18-CE17-0028,HuMABK,Les anticorps monoclonaux humains : une Nouvelle approche thérapeutique contre l'infection par le virus BK et les maladies associées(2018), ANR-11-LABX-0070,TRANSPLANTEX,Nouveaux loci d'histocompatibilité/biomarqueurs en transplantation humaine: de la découverte à l'app(2011), Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM), Virus et Immunité - Virus and immunity (CNRS-UMR3569), Vaccine Research Institute [Créteil, France] (VRI), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), and HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Paris Cité (UPCité)-Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM)
Subjects: Male, Medicine (General), Time Factors, Antibodies, Viral, Neutralization, Immunoglobulin G, 0302 clinical medicine, Medicine, Longitudinal Studies, Prospective Studies, Prospective cohort study, 0303 health sciences, biology, Incidence (epidemiology), Antibody titer, General Medicine, Middle Aged, 3. Good health, Vaccination, Titer, 030220 oncology & carcinogenesis, Spike Glycoprotein, Coronavirus, Female, Antibody, Research Paper, Adult, COVID-19 Vaccines, Neutralizing antibodies, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, R5-920, Coronavirus Nucleocapsid Proteins, Humans, 030304 developmental biology, business.industry, SARS-CoV-2, Immunity, COVID-19, Phosphoproteins, Antibodies, Neutralizing, Immunity, Humoral, Kinetics, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Reinfection, Immunology, biology.protein, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business
Abstract: Background Assessment of the kinetics of SARS-CoV-2 antibodies is essential in predicting risk of reinfection and durability of vaccine protection. Methods This is a prospective, monocentric, longitudinal, cohort clinical study. Healthcare workers (HCW) from Strasbourg University Hospital were enrolled between April 6th and May 7th, 2020 and followed up to 422 days. Serial serum samples were tested for antibodies against the Receptor Binding Domain (RBD) of the spike protein and nucleocapsid protein (N) to characterize the kinetics of SARS-CoV-2 antibodies and the incidence of reinfection. Live-neutralization assays were performed for a subset of samples before and after vaccination to analyze sensitivity to SARS-CoV-2 variants. Findings A total of 4290 samples from 393 convalescent COVID-19 and 916 COVID-19 negative individuals were analyzed. In convalescent individuals, SARS-CoV-2 antibodies followed a triphasic kinetic model with half-lives at month (M) 11–13 of 283 days (95% CI 231–349) for anti-N and 725 days (95% CI 623–921) for anti-RBD IgG, which stabilized at a median of 1.54 log BAU/mL (95% CI 1.42–1.67). The incidence of SARS-CoV-2 infections was 12.22 and 0.40 per 100 person-years in COVID-19-negative and COVID-19-positive HCW, respectively, indicating a relative reduction in the incidence of SARS-CoV-2 reinfection of 96.7%. Live-virus neutralization assay revealed that after one year, variants D614G and B.1.1.7, but less so B.1.351, were sensitive to anti-RBD antibodies at 1.4 log BAU/mL, while IgG ≥ 2.0 log BAU/mL strongly neutralized all three variants. These latter anti-RBD IgG titers were reached by all vaccinated HCW regardless of pre-vaccination IgG levels and type of vaccine. Interpretation Our study demonstrates a long-term persistence of anti-RBD antibodies that may reduce risk of reinfection. By significantly increasing cross-neutralizing antibody titers, a single-dose vaccination strengthens protection against variants., Graphical abstract Image, graphical abstract
Published: 2021
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45. Rapid decline of neutralizing antibodies against SARS-CoV-2 among infected healthcare workers

Author: Marot, Stéphane, Malet, Isabelle, Leducq, Valentin, Zafilaza, Karen, Sterlin, Delphine, Planas, Delphine, Gothland, Adélie, Jary, Aude, Dorgham, Karim, Bruel, Timothée, Attali, Valérie, Baresse, Isabelle, Beurton, Alexandra, Boddaert, Jacques, Bourmaleau, Julie, Catala, Martin, Demoule, Alexandre, Dunoyer, Violaine, Esteban-Amarilla, Cristina, Hausfater, Pierre, Haziot, Noémie, Ip, Queyras, Kubis, Nathalie, Lhoest, Laurence, Lubetzki, Catherine, Marion, Fabienne, Morawiec, Elise, Mourtada, Leila, Orcel, Brigitte, Morelot-Panzini, Capucine, Raux, Mathieu, Reinhard, Christophe, Riquier, Claire, Roubertier, Xavier, Weiss, Nicolas, Zalc, Bernard, Burrel, Sonia, Boutolleau, David, Schwartz, Olivier, Gorochov, Guy, Calvez, Vincent, Marcelin, Anne-Geneviève, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Anticorps en thérapie et pathologie - Antibodies in Therapy and Pathology, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris], Centre d'Immunologie et de Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Vaccine Research Institute (VRI), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Virus et Immunité - Virus and immunity, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), The AGM laboratory is funded by Agence Nationale de Recherches sur le SIDA et les hépatites virales (AC43, Medical Virology), the SARS-CoV-2 Program of the Faculty of Medicine of Sorbonne University, the Agence Nationale de la Recherche. The GG laboratory is supported by the Fondation de France, 'Tous unis contre le virus' framework Alliance (Fondation de France, AP-HP, Institut Pasteur) in collaboration with the Agence Nationale de la Recherche (ANR Flash COVID19 program) and by the SARS-CoV-2 Program of the Faculty of Medicine of Sorbonne University ICOViD programs. The OS laboratory is funded by Institut Pasteur, the ANRS, the Vaccine Research Institute (ANR-10-LABX-77), Labex IBEID (ANR-10-LABX-62-IBEID), 'TIMTAMDEN' ANR-14-CE14-0029, 'CHIKV-Viro-Immuno' ANR-14-CE14-0015-01, the Gilead HIV cure program, ANR/FRM Flash Covid PROTEO-SARS-CoV-2 and IDISCOVR, and Fondation pour la Recherche Médicale. We thank Nathalie Aulner and the UtechS Photonic BioImaging (UPBI) core facility (Institut Pasteur), a member of the France BioImaging network, for image acquisition and analysis., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-10-LABX-0077,VRI,Initiative for the creation of a Vaccine Research Institute(2010), ANR-14-CE14-0029,TIMTAMDEN,Rôle des récepteurs TIM et TAM dans l'infection des cellules cibles par le virus de la dengue(2014), ANR-14-CE14-0015,CHIKV-Viro-Immuno,Multiplication et Relation avec l'hôte du virus Chikungunya(2014), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Immunologie et des Maladies Infectieuses (CIMI), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Vaccine Research Institute [Créteil, France] (VRI), Virus et Immunité - Virus and immunity (CNRS-UMR3569), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), HAL-SU, Gestionnaire, Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - VALID, Laboratoires d'excellence - Initiative for the creation of a Vaccine Research Institute - - VRI2010 - ANR-10-LABX-0077 - LABX - VALID, Appel à projets générique - Rôle des récepteurs TIM et TAM dans l'infection des cellules cibles par le virus de la dengue - - TIMTAMDEN2014 - ANR-14-CE14-0029 - Appel à projets générique - VALID, and Appel à projets générique - Multiplication et Relation avec l'hôte du virus Chikungunya - - CHIKV-Viro-Immuno2014 - ANR-14-CE14-0015 - Appel à projets générique - VALID
Subjects: 0301 basic medicine, Immunoglobulin A, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Science, General Physics and Astronomy, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, Article, General Biochemistry, Genetics and Molecular Biology, Persistence (computer science), 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Medicine, Infection control, 030212 general & internal medicine, [SDV.IMM.II] Life Sciences [q-bio]/Immunology/Innate immunity, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Multidisciplinary, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, biology, business.industry, SARS-CoV-2, General Chemistry, biochemical phenomena, metabolism, and nutrition, 3. Good health, Vaccination, Titer, 030104 developmental biology, Viral infection, Immunology, biology.protein, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, sense organs, Antibody, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: There are only few data concerning persistence of neutralizing antibodies (NAbs) among SARS-CoV-2-infected healthcare workers (HCW). These individuals are particularly exposed to SARS-CoV-2 infection and at potential risk of reinfection. We followed 26 HCW with mild COVID-19 three weeks (D21), two months (M2) and three months (M3) after the onset of symptoms. All the HCW had anti-receptor binding domain (RBD) IgA at D21, decreasing to 38.5% at M3 (p, The humoral immune response to SARS-CoV-2 infection is not yet fully understood. Here, Marot et al. monitor the longitudinal profile and neutralizing activity of IgG, IgA, and IgM among 26 healthcare workers and provide evidence for a short-lasting humoral immune protection due to a decrease of neutralizing antibody titers within 3 months.
Published: 2021
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46. Effective Anti–SARS-CoV-2 Immune Response in Patients With Clonal Mast Cell Disorders

Author: Julien Rossignol, Amani Ouedrani, Cristina Bulai Livideanu, Stéphane Barete, Louis Terriou, David Launay, Richard Lemal, Celine Greco, Laurent Frenzel, Cecile Meni, Christine Bodemere-Skandalis, Laura Polivka, Anne-Florence Collange, Hassiba Hachichi, Sonia Bouzourine, Djazira Nait Messaoud, Mathilde Negretto, Laurence Vendrame, Marguerite Jambou, Marie Gousseff, Stéphane Durupt, Jean-Christophe Lega, Jean-Marc Durand, Caroline Gaudy, Gandhi Damaj, Marie-Pierre Gourin, Mohamed Hamidou, Laurence Bouillet, Edwige Le Mouel, Alexandre Maria, Patricia Zunic, Quentin Cabrera, Denis Vincent, Christian Lavigne, Etienne Riviere, Clement Gourguechon, Marie Courbebaisse, David Lebeaux, Béatrice Parfait, Gérard Friedlander, Anne Brignier, Ludovic Lhermitte, Thierry Jo Molina, Julie Bruneau, Julie Agopian, Patrice Dubreuil, Dana Ranta, Alexandre Mania, Michel Arock, Isabelle Staropoli, Olivier Tournilhac, Olivier Lortholary, Olivier Schwartz, Lucienne Chatenoud, Olivier Hermine, Centre de référence des mastocytoses (CEREMAST), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Référence des Mastocytoses de Toulouse (CEREMAST), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institute for Translational Research in Inflammation - U 1286 (INFINITE (Ex-Liric)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias (CHELTER), Université Clermont Auvergne (UCA), Virus et Immunité - Virus and immunity (CNRS-UMR3569), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), The authors would like to thank Fondation Université de Paris, AXA research fund, Fondation Hôpitaux de Paris-Hôpitaux de France, Mécénat du GH APHP. CUP, Fondation pour la Recherche en Physiologie and DMU BioPhyGen for the funding of the COVID-HOP study., ANR-20-COV1-0001,APCOD,Les cellules présentatrices d'antigènes dans la maladie de COVID-19 à résolution monocellulaire(2020), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPC), CHU Toulouse [Toulouse], Virus et Immunité - Virus and immunity, and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)
Subjects: PBMC, peripheral blood mononuclear cell, BMI, body mass index, T cells, B-cells, CEREMAST, Centre de Référence des Mastocytoses, CM, cutaneous mastocytosis, MMAS, monoclonal mast cell activation syndrome, PHA, phytohemagglutinin, PMSI, Programme de médicalisation des systèmes d'information, Antibodies, Viral, SARS-CoV-2, severe acute respiratory syndrome coronavirus 2, Antiviral Agents, WHO, World Health Organization, MIS, mastocytosis in the skin, HEK, human embryonic kidney, Humans, Immunology and Allergy, IFN, interferon, Mast Cells, APHP, Assistance Publique - Hôpitaux de Paris (Paris Public Hospital Group), B cells, SARS-CoV-2, T-cells, Immunity, COVID-19, ISM, indolent systemic mastocytosis, Clonal mast cell activation syndrome, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, MCAS, mast cell activation syndrome, Original Article, Mast cell activation dis- orders, SSM, smoldering systemic mastocytosis, NK, natural killer, Mastocytosis, COVID-19, coronavirus disease 19, Mast cell activation disorders, cMCAD, clonal mast cell activation disorder
Abstract: International audience; BackgroundMast cells are key players in innate immunity and the TH2 adaptive immune response. The latter counterbalances the TH1 response, which is critical for antiviral immunity. Clonal mast cell activation disorders (cMCADs, such as mastocytosis and clonal mast cell activation syndrome) are characterized by abnormal mast cell accumulation and/or activation. No data on the antiviral immune response in patients with MCADs have been published.ObjectiveTo study a comprehensive range of outcomes in patients with cMCAD with PCR- or serologically confirmed coronavirus disease 2019 and to characterize the specific anti–severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immune response in this setting.MethodsClinical follow-up and outcome data were collected prospectively over a 12-month period by members of the French Centre de Référence des Mastocytoses rare disease network. Anti–SARS-CoV-2–specific T-cell activity was measured with an ELISA, and humoral responses were evaluated by assaying circulating levels of specific IgG, IgA, and neutralizing antibodies.ResultsOverall, 32 patients with cMCAD were evaluated. None required noninvasive or mechanical ventilation. Two patients were admitted to hospital for oxygen and steroid therapy. The SARS-CoV-2–specific immune response was characterized in 21 of the 32 patients. Most had high counts of circulating SARS-CoV-2–specific, IFN-γ–producing T cells and high titers of neutralizing antispike IgGs. The patients frequently showed spontaneous T-cell IFN-γ production in the absence of stimulation; this production was correlated with basal circulating tryptase levels (a marker of the mast cell burden).ConclusionsPatients with cMCADs might not be at risk of severe coronavirus disease 2019, perhaps due to their spontaneous production of IFN-γ.
Published: 2022
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47. Extracellular vesicles containing ACE2 efficiently prevent infection by SARS‐CoV‐2 Spike protein‐containing virus

Author: Nicolas Manel, Clotilde Théry, Olivier Schwartz, Federico Cocozza, Nathalie Névo, Mercedes Tkach, Julian Buchrieser, Xavier Lahaye, Lorena Martin-Jaular, Ester Piovesana, Immunité et cancer (U932), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Curie [Paris], Université Paris sciences et lettres (PSL), Virus et Immunité - Virus and immunity, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Université de Paris (UP), This work was supported by Institut Curie, INSERM, CNRS, grants H2020-MSCA-ITN (722148, TRAIN-EV), INCa (11548) and Fondation ARC (PGA1 RF20180206962) to C Théry, LABEX DCBIOL (ANR-10-IDEX-0001-02 PSL* and ANR-11-LABX-0043) to C. Théry and N. Manel, LABEX VRI (ANR-10-LABX-77), ANRS (France Recherche Nord & Sud Sida-HIV Hépatites, ECTZ36691, ECTZ71745), Sidaction (17-1-AAE-11097-2), ANR (ANR-19-CE15-0018-01, ANR-18-CE92-0022-01), DIM1HEALTH to N Manel. N Manel thanks Mutuelle Bleue for support., ANR-10-IDEX-0001,PSL,Paris Sciences et Lettres(2010), ANR-11-LABX-0043,DCBIOL,Biologie des cellules dendritiques(2011), ANR-10-LABX-0077,VRI,Initiative for the creation of a Vaccine Research Institute(2010), ANR-19-CE15-0018,NUCLEONDRIA,Fonctions émergentes du détection de l'immunité innée cGAS dans les organites à ADN(2019), ANR-18-CE92-0022,cGAS-Vac,Analyses fonctionnelles de la voie cGAS/STING au cours d'infections bactériennes et infections virales et implications pour le développement de vaccins innovants(2018), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Cité (UPCité), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), LAHAYE, Xavier, Initiative d'excellence - Paris Sciences et Lettres - - PSL2010 - ANR-10-IDEX-0001 - IDEX - VALID, Biologie des cellules dendritiques - - DCBIOL2011 - ANR-11-LABX-0043 - LABX - VALID, Laboratoires d'excellence - Initiative for the creation of a Vaccine Research Institute - - VRI2010 - ANR-10-LABX-0077 - LABX - VALID, Fonctions émergentes du détection de l'immunité innée cGAS dans les organites à ADN - - NUCLEONDRIA2019 - ANR-19-CE15-0018 - AAPG2019 - VALID, APPEL À PROJETS GÉNÉRIQUE 2018 - Analyses fonctionnelles de la voie cGAS/STING au cours d'infections bactériennes et infections virales et implications pour le développement de vaccins innovants - - cGAS-Vac2018 - ANR-18-CE92-0022 - AAPG2018 - VALID, and Virus et Immunité - Virus and immunity (CNRS-UMR3569)
Subjects: 0301 basic medicine, Histology, [SDV.IMM] Life Sciences [q-bio]/Immunology, Short Communication, viruses, Priming (immunology), ACE2, urologic and male genital diseases, TMPRSS2, Virus, SARS‐CoV‐2, Cell Line, 03 medical and health sciences, Extracellular Vesicles, 0302 clinical medicine, Humans, Receptor, skin and connective tissue diseases, Infectivity, Innate immune system, biology, Chemistry, SARS-CoV-2, Lentivirus, Serine Endopeptidases, Lipid bilayer fusion, COVID-19, Cell Biology, Virus Internalization, biology.organism_classification, Cell biology, 030104 developmental biology, 030220 oncology & carcinogenesis, Spike Glycoprotein, Coronavirus, Receptors, Virus, [SDV.IMM]Life Sciences [q-bio]/Immunology, Angiotensin-Converting Enzyme 2, EV therapy, Caco-2 Cells, hormones, hormone substitutes, and hormone antagonists
Abstract: International audience; SARS-CoV-2 entry is mediated by binding of the spike protein (S) to the surface receptor ACE2 and subsequent priming by host TMPRSS2 allowing membrane fusion. Here, we produced extracellular vesicles (EVs) exposing ACE2 and demonstrate that ACE2-EVs are efficient decoys for SARS-CoV-2 S protein-containing lentivirus. Reduction of infectivity positively correlates with the level of ACE2, is much more efficient than with soluble ACE2 and further enhanced by the inclusion of TMPRSS2.
Published: 2020
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48. Syncytia formation by SARS‐CoV‐2‐infected cells

Author: Julian Buchrieser, Olivier Schwartz, Sylvie van der Werf, Cyril Planchais, Mathieu Hubert, Jérémy Dufloo, Maaran Michael Rajah, Blandine Monel, Nicoletta Casartelli, Delphine Planas, Hugo Mouquet, Florence Guivel-Benhassine, Timothée Bruel, Françoise Porrot, Virus et Immunité - Virus and immunity, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), École Doctorale Bio Sorbonne Paris Cité [Paris] (ED BioSPC), Université Sorbonne Paris Cité (USPC)-Université de Paris (UP), Vaccine Research Institute (VRI), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Immunologie humorale - Humoral Immunology, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Génétique Moléculaire des Virus à ARN - Molecular Genetics of RNA Viruses (GMV-ARN (UMR_3569 / U-Pasteur_2)), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Centre National de Référence des virus des infections respiratoires (dont la grippe) - National Reference Center Virus Influenzae [Paris] (CNR), Institut Pasteur [Paris], OS laboratory is funded by Institut Pasteur, ANRS, the Vaccine Research Institute (ANR-10-LABX-77), Labex IBEID (ANR-10-LABX-62-IBEID), 'TIMTAMDEN' ANR-14-CE14-0029, 'CHIKV-Viro-Immuno' ANR-14-CE14-0015-01 and the Gilead HIV cure program, ANR/FRM Flash Covid PROTEO-SARS-CoV-2 and IDISCOVR. Work in UPBI is funded by grant ANR-10-INSB-04-01 and Région Ile-de-France program DIM1-Health. HM laboratory is funded by the Institut Pasteur, the Milieu Intérieur Program (ANR-10-LABX-69-01), the INSERM, REACTing, and EU (RECOVER) grants. SVDW laboratory is funded by Institut Pasteur, CNRS, Université de Paris, Santé publique France, Labex IBEID (ANR-10-LABX-62-IBEID), REACTing, and EU (RECOVER) grant. M.M.R is supported by the Pasteur-Paris University (PPU) International Doctoral Program., ANR-10-LABX-0077,VRI,Initiative for the creation of a Vaccine Research Institute(2010), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-14-CE14-0029,TIMTAMDEN,Rôle des récepteurs TIM et TAM dans l'infection des cellules cibles par le virus de la dengue(2014), ANR-14-CE14-0015,CHIKV-Viro-Immuno,Multiplication et Relation avec l'hôte du virus Chikungunya(2014), ANR-10-INBS-0004,France-BioImaging,Développment d'une infrastructure française distribuée coordonnée(2010), ANR-10-LABX-0069,MILIEU INTERIEUR,GENETIC & ENVIRONMENTAL CONTROL OF IMMUNE PHENOTYPE VARIANCE: ESTABLISHING A PATH TOWARDS PERSONALIZED MEDICINE(2010), École Doctorale Bio Sorbonne Paris Cité [Paris] (ED562 - BioSPC), Université Sorbonne Paris Cité (USPC)-Université Paris Cité (UPCité), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), CASARTELLI, NICOLETTA, Laboratoires d'excellence - Initiative for the creation of a Vaccine Research Institute - - VRI2010 - ANR-10-LABX-0077 - LABX - VALID, Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - VALID, Appel à projets générique - Rôle des récepteurs TIM et TAM dans l'infection des cellules cibles par le virus de la dengue - - TIMTAMDEN2014 - ANR-14-CE14-0029 - Appel à projets générique - VALID, Appel à projets générique - Multiplication et Relation avec l'hôte du virus Chikungunya - - CHIKV-Viro-Immuno2014 - ANR-14-CE14-0015 - Appel à projets générique - VALID, Développment d'une infrastructure française distribuée coordonnée - - France-BioImaging2010 - ANR-10-INBS-0004 - INBS - VALID, Laboratoires d'excellence - GENETIC & ENVIRONMENTAL CONTROL OF IMMUNE PHENOTYPE VARIANCE: ESTABLISHING A PATH TOWARDS PERSONALIZED MEDICINE - - MILIEU INTERIEUR2010 - ANR-10-LABX-0069 - LABX - VALID, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut Pasteur [Paris] (IP), Virus et Immunité - Virus and immunity (CNRS-UMR3569), Vaccine Research Institute [Créteil, France] (VRI), and Centre National de Référence des virus des infections respiratoires (dont la grippe) - National Reference Center Virus Influenzae [Paris] (CNR - laboratoire coordonnateur)
Subjects: fusion, viruses, MESH: Spike Glycoprotein, Coronavirus, MESH: Angiotensin-Converting Enzyme 2, Giant Cells, SARS‐CoV‐2, Cell Fusion, MESH: Giant Cells, 0302 clinical medicine, Interferon, MESH: Chlorocebus aethiops, Chlorocebus aethiops, MESH: COVID-19, MESH: Animals, MESH: Serine Endopeptidases, ComputingMilieux_MISCELLANEOUS, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Syncytium, 0303 health sciences, Cell fusion, General Neuroscience, Serine Endopeptidases, RNA-Binding Proteins, Articles, interferon, Transmembrane protein, Cell biology, 3. Good health, 030220 oncology & carcinogenesis, MESH: HEK293 Cells, MESH: Antigens, Differentiation, Host-Pathogen Interactions, Spike Glycoprotein, Coronavirus, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, Angiotensin-Converting Enzyme 2, MESH: Membrane Proteins, Corrigendum, medicine.drug, Immunology, ComputingMethodologies_IMAGEPROCESSINGANDCOMPUTERVISION, MESH: Vero Cells, Biology, Article, General Biochemistry, Genetics and Molecular Biology, Cell Line, 03 medical and health sciences, medicine, Animals, Humans, MESH: SARS-CoV-2, syncytia, Vero Cells, Molecular Biology, 030304 developmental biology, MESH: Humans, General Immunology and Microbiology, SARS-CoV-2, HEK 293 cells, MESH: Host-Pathogen Interactions, COVID-19, Membrane Proteins, biochemical phenomena, metabolism, and nutrition, Antigens, Differentiation, MESH: Cell Line, HEK293 Cells, MESH: RNA-Binding Proteins, Membrane protein, Cell culture, MESH: Cell Fusion, Vero cell, 030217 neurology & neurosurgery
Abstract: Severe cases of COVID‐19 are associated with extensive lung damage and the presence of infected multinucleated syncytial pneumocytes. The viral and cellular mechanisms regulating the formation of these syncytia are not well understood. Here, we show that SARS‐CoV‐2‐infected cells express the Spike protein (S) at their surface and fuse with ACE2‐positive neighboring cells. Expression of S without any other viral proteins triggers syncytia formation. Interferon‐induced transmembrane proteins (IFITMs), a family of restriction factors that block the entry of many viruses, inhibit S‐mediated fusion, with IFITM1 being more active than IFITM2 and IFITM3. On the contrary, the TMPRSS2 serine protease, which is known to enhance infectivity of cell‐free virions, processes both S and ACE2 and increases syncytia formation by accelerating the fusion process. TMPRSS2 thwarts the antiviral effect of IFITMs. Our results show that SARS‐CoV‐2 pathological effects are modulated by cellular proteins that either inhibit or facilitate syncytia formation., Cells infected with SARS‐CoV‐2 can fuse with neighbouring cells in a process accelerated by infectivity‐enhancing host factor TMPRSS2 and restricted by antiviral IFITM proteins.
Published: 2020
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49. IgA dominates the early neutralizing antibody response to SARS-CoV-2

Author: Pierre Charneau, Jean Marc Lacorte, Laetitia Claër, Olivier Schwartz, Amélie Guihot, Cary Gunn, Rick Hockett, Pascale Ghillani, Hans Yssel, Alexis Mathian, Jehane Fadlallah, Timothée Bruel, Karim Dorgham, Paul Quentric, François Anna, Makoto Miyara, Salma Fourati, Charles Edouard Luyt, Guy Gorochov, Delphine Sterlin, Hervé Devilliers, Sasi Mudumba, Alexandra Beurton, Julien Mayaux, Zahir Amoura, Christophe Parizot, Audrey Mohr, Anticorps en thérapie et pathologie - Antibodies in Therapy and Pathology, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Immunologie et des Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Virologie Moléculaire et Vaccinologie / Molecular Virology and Vaccinology, Institut Pasteur [Paris], Laboratoire commun Pasteur-TheraVectys, Institut Pasteur [Paris]-TheraVectys, Service de Médecine Interne (SOC 1 et SOC 2) [CHU de Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service d'Immunologie [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'Anesthésie réanimation [CHU Pitié-Salpêtrière], Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases [IHU ICAN], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Service de Pneumologie et Réanimation Médicale [CHU Pitié-Salpêtrière] (Département ' R3S '), Neurophysiologie Respiratoire Expérimentale et Clinique (UMRS 1158), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service de Biochimie Endocrinienne et Oncologie [CHU Pitié-Salpêtrière], Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Virus et Immunité - Virus and immunity, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Vaccine Research Institute (VRI), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service de médecine interne [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris] (IP), Institut Pasteur [Paris] (IP)-TheraVectys, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Virus et Immunité - Virus and immunity (CNRS-UMR3569), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Vaccine Research Institute [Créteil, France] (VRI), ANR-20-COVI-0025,iCovid,Immunopathologie du COVID-19 à l'Assistance Publique Hôpitaux de Paris(2020), Centre d'Immunologie et de Maladies Infectieuses (CIMI), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Neurophysiologie Respiratoire Expérimentale et Clinique, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), and Gestionnaire, HAL Sorbonne Université 5
Subjects: Saliva, Time Factors, viruses, Antibodies, Viral, Immunoglobulin E, 03 medical and health sciences, 0302 clinical medicine, Immune system, Immunity, Humans, Medicine, Longitudinal Studies, Neutralizing antibody, Research Articles, 030304 developmental biology, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, 0303 health sciences, biology, SARS-CoV-2, business.industry, Case-control study, COVID-19, General Medicine, Antibodies, Neutralizing, Primary and secondary antibodies, STM r-articles, Immunity, Humoral, Immunoglobulin A, 3. Good health, Coronavirus, Immunoglobulin M, Case-Control Studies, Immunoglobulin G, 030220 oncology & carcinogenesis, Host-Pathogen Interactions, Immunology, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, biology.protein, Antibody, business, Bronchoalveolar Lavage Fluid, Biomarkers, Research Article
Abstract: Early specific antibody responses against SARS-CoV-2 include IgG, IgM, and IgA, but IgA may neutralize virus and control infection to a larger extent., Early action of IgA Humoral immune responses play a critical role in protecting individuals against SARS-CoV-2 infection, particularly through the activity of neutralizing antibodies. Sterlin et al. measured humoral immune responses in the serum, saliva, and bronchoalveolar lavage fluid of SARS-CoV-2–infected patients who experienced a range of COVID-19 disease severity. IgA antibodies dominated the early SARS-CoV-2–specific antibody response compared with IgG and IgM concentrations in these fluids and was associated with expansion of IgA plasmablasts with mucosal homing characteristics. IgA serum concentrations peaked 3 weeks after symptom onset but persisted for several more weeks in saliva, and serum IgA was more potent than IgG in neutralizing SARS-CoV-2. These findings highlight the potential role of IgA during early SARS-CoV-2 infection., Humoral immune responses are typically characterized by primary IgM antibody responses followed by secondary antibody responses associated with immune memory and composed of IgG, IgA, and IgE. Here, we measured acute humoral responses to SARS-CoV-2, including the frequency of antibody-secreting cells and the presence of SARS-CoV-2–specific neutralizing antibodies in the serum, saliva, and bronchoalveolar fluid of 159 patients with COVID-19. Early SARS-CoV-2–specific humoral responses were dominated by IgA antibodies. Peripheral expansion of IgA plasmablasts with mucosal homing potential was detected shortly after the onset of symptoms and peaked during the third week of the disease. The virus-specific antibody responses included IgG, IgM, and IgA, but IgA contributed to virus neutralization to a greater extent compared with IgG. Specific IgA serum concentrations decreased notably 1 month after the onset of symptoms, but neutralizing IgA remained detectable in saliva for a longer time (days 49 to 73 post-symptoms). These results represent a critical observation given the emerging information as to the types of antibodies associated with optimal protection against reinfection and whether vaccine regimens should consider targeting a potent but potentially short-lived IgA response.
Published: 2020
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50. Asymptomatic and symptomatic SARS-CoV-2 infections elicit polyfunctional antibodies

Author: Stéphane Pelleau, François Anna, Michael T. White, Pierre Charneau, Arnaud Fontanet, Timothée Bruel, Hugo Mouquet, Bruno Hoen, Yoann Madec, Jérémy Dufloo, Yves Levy, Ludivine Grzelak, Isabelle Staropoli, Marie-Noëlle Ungeheuer, Laura Tondeur, Rémy Robinot, Julian Buchrieser, Aurélie Wiedemann, Cyril Planchais, Olivier Schwartz, Virus et Immunité - Virus and immunity, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Université Sorbonne Paris Cité (USPC), Epidémiologie des Maladies Emergentes - Emerging Diseases Epidemiology, Pasteur-Cnam Risques infectieux et émergents (PACRI), Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM), Laboratoire commun Pasteur-TheraVectys, Institut Pasteur [Paris]-TheraVectys, Malaria : parasites et hôtes - Malaria : parasites and hosts, Institut Pasteur [Paris], Vaccine Research Institute (VRI), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Immunologie humorale - Humoral Immunology, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Investigation Clinique et d’Accès aux Ressources Biologiques (Plate-forme) - Clinical Investigation and Access to BioResources (ICAReB), Virologie Moléculaire et Vaccinologie / Molecular Virology and Vaccinology, Direction de la recherche médicale de l'Institut Pasteur, Conservatoire National des Arts et Métiers [CNAM] (CNAM), This work was supported by the Urgence COVID-19 Fundraising Campaign of Institut Pasteur. O.S. is funded by Institut Pasteur, ANRS, Sidaction, the Vaccine Research Institute (ANR-10-LABX-77), Labex IBEID (ANR-10-LABX-62-IBEID), the 'TIMTAMDEN' project (a collaboration of Inserm, Institut Pasteur, and IRD, ANR-14-CE14-0029), the ANR 'CHIKV-Viro-Immuno' project (ANR-14-CE14-0015-01), and the Gilead HIV cure program. J.D. and L.G. are supported by the French Ministry of Higher Education, Research and Innovation. H.M. is funded by the Institut Pasteur, the Milieu Intérieur Program (ANR-10-LABX-69-01), Inserm, and REACTing and EU RECOVER grants. C.P. is supported by a fellowship from the Agence Nationale de Recherches sur le Sida et les Hépatites Virales (ANRS)., ANR-10-LABX-0077,VRI,Initiative for the creation of a Vaccine Research Institute(2010), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-14-CE14-0029,TIMTAMDEN,Rôle des récepteurs TIM et TAM dans l'infection des cellules cibles par le virus de la dengue(2014), ANR-14-CE14-0015,CHIKV-Viro-Immuno,Multiplication et Relation avec l'hôte du virus Chikungunya(2014), ANR-10-LABX-0069,MILIEU INTERIEUR,GENETIC & ENVIRONMENTAL CONTROL OF IMMUNE PHENOTYPE VARIANCE: ESTABLISHING A PATH TOWARDS PERSONALIZED MEDICINE(2010), Virus et Immunité - Virus and immunity (CNRS-UMR3569), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), Institut Pasteur [Paris] (IP)-TheraVectys, Institut Pasteur [Paris] (IP), Vaccine Research Institute [Créteil, France] (VRI), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM), and HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM)
Subjects: Male, Medicine (General), [SDV]Life Sciences [q-bio], Cell, Antibodies, Viral, Severity of Illness Index, Epitope, Immunoglobulin G, Neutralization, Antigen-Antibody Reactions, Epitopes, 0302 clinical medicine, antibody, Medicine, complement, Antibody-dependent cell-mediated cytotoxicity, 0303 health sciences, biology, Middle Aged, 3. Good health, Killer Cells, Natural, medicine.anatomical_structure, Spike Glycoprotein, Coronavirus, Female, medicine.symptom, Antibody, ADCC, Adult, Adolescent, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Asymptomatic, General Biochemistry, Genetics and Molecular Biology, Article, Virus, Young Adult, 03 medical and health sciences, R5-920, Neutralization Tests, Humans, asymptomatic, 030304 developmental biology, SARS-CoV-2, business.industry, Antibody-Dependent Cell Cytotoxicity, COVID-19, Complement System Proteins, Asymptomatic Diseases, Immunology, biology.protein, business, 030217 neurology & neurosurgery
Abstract: A large proportion of SARS-CoV-2 infected individuals remains asymptomatic. Little is known about the extent and quality of their antiviral humoral response. Here, we analyze antibody functions in 52 asymptomatic infected individuals, 119 mild and 21 hospitalized COVID-19 patients. We measured anti-Spike IgG, IgA and IgM levels with the S-Flow assay and map IgG-targeted epitopes by Luminex. We also evaluated neutralization, complement deposition and Antibody-Dependent Cellular Cytotoxicity (ADCC) using replication-competent SARS-CoV-2 or reporter cell systems. We show that COVID-19 sera mediate complement deposition and kill infected cells by ADCC. Sera from asymptomatic individuals neutralize the virus, activate ADCC and trigger complement deposition. Antibody levels and functions are lower in asymptomatic individuals than in symptomatic cases. Antibody functions are correlated, regardless of disease severity. Longitudinal samplings show that antibody functions follow similar kinetics of induction and contraction. Overall, asymptomatic SARS-CoV-2 infection elicits polyfunctional antibodies neutralizing the virus and targeting infected cells., Graphical Abstract, Dufloo et al. show that SARS-CoV-2 infection elicits antibodies that neutralize the virus, activate the complement system and kill infected cells by ADCC. These polyfunctional antibodies are slightly more abundant in symptomatic COVID-19 patients than in asymptomatic individuals and correlate with disease severity.
Published: 2020
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