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2. TMPRSS2 is a functional receptor for human coronavirus HKU1

Author

Saunders, Nell, Fernandez, Ignacio, Planchais, Cyril, Michel, Vincent, Rajah, Maaran Michael, Baquero Salazar, Eduard, Postal, Jeanne, Porrot, Francoise, Guivel-Benhassine, Florence, Blanc, Catherine, Chauveau-Le Friec, Gaëlle, Martin, Augustin, Grzelak, Ludivine, Oktavia, Rischa Maya, Meola, Annalisa, Ahouzi, Olivia, Hoover-Watson, Hunter, Prot, Matthieu, Delaune, Deborah, Cornelissen, Marion, Deijs, Martin, Meriaux, Véronique, Mouquet, Hugo, Simon-Lorière, Etienne, van der Hoek, Lia, Lafaye, Pierre, Rey, Felix, Buchrieser, Julian, and Schwartz, Olivier

Published
2023
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3. A synthetic delivery vector for mucosal vaccination

Author

Billet, Anne, Hadjerci, Justine, Tran, Thi, Kessler, Pascal, Ulmer, Jonathan, Mourier, Gilles, Ghazarian, Marine, Gonzalez, Anthony, Thai, Robert, Urquia, Pauline, Van Baelen, Anne-Cécile, Meola, Annalisa, Fernandez, Ignacio, Deville-Foillard, Stéphanie, MacDonald, Ewan, Paolini, Léa, Schmidt, Frédéric, Rey, Félix A., Kay, Michael S., Tartour, Eric, Servent, Denis, and Johannes, Ludger

Published
2023
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4. SARS-CoV-2 Omicron BA.1 breakthrough infection drives late remodeling of the memory B cell repertoire in vaccinated individuals

Author

Sokal, Aurélien, Barba-Spaeth, Giovanna, Hunault, Lise, Fernández, Ignacio, Broketa, Matteo, Meola, Annalisa, Fourati, Slim, Azzaoui, Imane, Vandenberghe, Alexis, Lagouge-Roussey, Pauline, Broutin, Manon, Roeser, Anais, Bouvier-Alias, Magali, Crickx, Etienne, Languille, Laetitia, Fournier, Morgane, Michel, Marc, Godeau, Bertrand, Gallien, Sébastien, Melica, Giovanna, Nguyen, Yann, Canoui-Poitrine, Florence, Pirenne, France, Megret, Jérôme, Pawlotsky, Jean-Michel, Fillatreau, Simon, Reynaud, Claude-Agnès, Weill, Jean-Claude, Rey, Félix A., Bruhns, Pierre, Mahévas, Matthieu, and Chappert, Pascal

Published
2023
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5. Modulation of SARS-CoV-2 spike binding to ACE2 through conformational selection

Author

Saha, Prithwidip, primary, Fernanadez, Ignacio, additional, Sumbul, Fidan, additional, Valotteau, Claire, additional, Kostrz, Dorota, additional, Meola, Annalisa, additional, Baquero, Eduard, additional, Sharma, Arvind, additional, Portman, James R., additional, Stransky, Francois, additional, Boudier, Thomas, additional, Guardado Calvo, Pablo, additional, Gosse, Charlie, additional, Strick, Terence, additional, Rey, Felix A., additional, and Rico, Felix, additional

Published
2024
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6. PLA2G1B is involved in CD4 anergy and CD4 lymphopenia in HIV-infected patients

Author

Pothlichet, Julien, Rose, Thierry, Bugault, Florence, Jeammet, Louise, Meola, Annalisa, Haouz, Ahmed, Saul, Frederick, Geny, David, Alcami, Jose, Ruiz-Mateos, Ezequiel, Teyton, Luc, Lambeau, Gerard, and Theze, Jacques

Subjects
HIV patients -- Physiological aspects, HIV infections -- Physiological aspects, Lymphocytopenia -- Physiological aspects, HIV -- Physiological aspects, Immunotherapy -- Physiological aspects, T cells -- Physiological aspects, Health care industry
Abstract

The precise mechanism leading to profound immunodeficiency of HIV-infected patients is still only partially understood. Here, we show that more than 80% of [CD4.sup.+] T cells from HIV-infected patients have morphological abnormalities. Their membranes exhibited numerous large abnormal membrane microdomains (aMMDs), which trap and inactivate physiological receptors, such as that for IL-7. In patient plasma, we identified phospholipase A2 group IB (PLA2G1B) as the key molecule responsible for the formation of aMMDs. At physiological concentrations, PLA2G1B synergized with the HIV gp41 envelope protein, which appears to be a driver that targets PLA2G1B to the [CD4.sup.+] T cell surface. The PLA2G1B/gp41 pair induced [CD4.sup.+] T cell unresponsiveness (anergy). At high concentrations in vitro, PLA2G1B acted alone, independently of gp41, and inhibited the IL-2, IL-4, and IL-7 responses, as well as TCR-mediated activation and proliferation, of [CD4.sup.+] T cells. PLA2G1B also decreased [CD4.sup.+] T cell survival in vitro, likely playing a role in CD4 lymphopenia in conjunction with its induced IL-7 receptor defects. The effects on [CD4.sup.+] T cell anergy could be blocked by a PLA2G1B- specific neutralizing mAb in vitro and in vivo. The PLA2G1B/gp41 pair constitutes what we believe is a new mechanism of immune dysfunction and a compelling target for boosting immune responses in HIV-infected patients., Introduction [CD4.sup.+] lymphocytes play a critical role in the severe immunodeficiency that characterizes HIV-infected patients. Although fewer than 0.5% of blood [CD4.sup.+] T cells are infected, almost all are dysfunctional. [...]

Published
2020
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7. Qualitative monitoring of SARS-CoV-2 mRNA vaccination in humans using droplet microfluidics

Author

Broketa, Matteo, primary, Sokal, Aurélien, additional, Mor, Michael, additional, Canales-Herrerias, Pablo, additional, Perima, Angga, additional, Meola, Annalisa, additional, Fernández, Ignacio, additional, Iannascoli, Bruno, additional, Chenon, Guilhem, additional, Vandenberghe, Alexis, additional, Languille, Laetitia, additional, Michel, Marc, additional, Godeau, Bertrand, additional, Gallien, Sébastien, additional, Melica, Giovanna, additional, Backovic, Marija, additional, Rey, Felix A., additional, Baudry, Jean, additional, Freund, Natalia T., additional, Mahévas, Matthieu, additional, and Bruhns, Pierre, additional

Published
2023
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8. A synthetic delivery vector for mucosal vaccination

Author

Billet, Anne, primary, Hadjerci, Justine, additional, Tran, Thi, additional, Kessler, Pascal, additional, Ulmer, Jonathan, additional, Mourier, Gilles, additional, Ghazarian, Marine, additional, Gonzalez, Anthony, additional, Thai, Robert, additional, Urquia, Pauline, additional, Vanbaelen, Anne-Cecile, additional, Meola, Annalisa, additional, Fernandez, Ignacio, additional, Deville-Foillard, Stephanie, additional, MacDonald, Ewan, additional, Paolini, Lea, additional, Schmidt, Frederic, additional, Rey, Felix A, additional, Kay, Michael S, additional, Tartour, Eric, additional, Servent, Denis, additional, and Johannes, Ludger, additional

Published
2023
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9. Omicron BA.1 breakthrough infection drives long-term remodeling of the memory B cell repertoire in vaccinated individuals

Author

Sokal, Aurélien, primary, Barba-Spaeth, Giovanna, additional, Hunault, Lise, additional, Fernández, Ignacio, additional, Broketa, Matteo, additional, Meola, Annalisa, additional, Fourati, Slim, additional, Azzaoui, Imane, additional, Vandenberghe, Alexis, additional, Lagouge-Roussey, Pauline, additional, Broutin, Manon, additional, Roeser, Anais, additional, Bouvier-Alias, Magali, additional, Crickx, Etienne, additional, Languille, Laetitia, additional, Fournier, Morgane, additional, Michel, Marc, additional, Godeau, Bertrand, additional, Gallien, Sébastien, additional, Melica, Giovanna, additional, Nguyen, Yann, additional, Canoui-Poitrine, Florence, additional, Noizat-Pirenne, France, additional, Megret, Jérôme, additional, Pawlotsky, Jean-Michel, additional, Fillatreau, Simon, additional, Reynaud, Claude-Agnès, additional, Weill, Jean-Claude, additional, Rey, Félix A., additional, Bruhns, Pierre, additional, Mahévas, Matthieu, additional, and Chappert, Pascal, additional

Published
2023
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10. Omicron BA.1 breakthrough infection drives long-term remodeling of the memory B cell repertoire in vaccinated individuals

Author

Sokal, Aurélien, Barba-Spaeth, Giovanna, Hunault, Lise, Fernández, Ignacio, Broketa, Matteo, Meola, Annalisa, Fourati, Slim, Azzaoui, Imane, Vandenberghe, Alexis, Lagouge-Roussey, Pauline, Broutin, Manon, Roeser, Anais, Bouvier-Alias, Magali, Crickx, Etienne, Languille, Laetitia, Fournier, Morgane, Michel, Marc, Godeau, Bertrand, Gallien, Sébastien, Melica, Giovanna, Nguyen, Yann, Canoui-Poitrine, Florence, Noizat-Pirenne, France, Megret, Jérôme, Pawlotsky, Jean-Michel, Fillatreau, Simon, Reynaud, Claude-Agnès, Weill, Jean-Claude, Rey, Félix, Bruhns, Pierre, Mahévas, Matthieu, Chappert, Pascal, 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), Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CIC - CHU Henri Mondor, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Virologie Structurale - Structural Virology, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Anticorps en thérapie et pathologie - Antibodies in Therapy and Pathology, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Physiologie, physiopathologie et thérapeutique (ED 394), Sorbonne Université (SU), 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 Henri Mondor [Créteil], 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), Hôpital Henri Mondor, Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Cochin [AP-HP], IMRB - CEPIA/'Clinical Epidemiology And Ageing : Geriatrics, Primary Care and Public Health' [Créteil] (U955 Inserm - UPEC), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Etablissement Français du Sang [Créteil], 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), and This work was funded by the CAPNET (Comité ad-hoc de pilotage national des essaisthérapeutiques et autres recherches, French government) and by the Fondation PrincesseGrace. Assistance Publique – Hôpitaux de Paris (AP-HP, Département de la Recherche Cli-nique et du Développement) was the promotor and sponsor of MEMO-COV-2. Work in theUnit of Structural Virology was funded by Institut Pasteur, Urgence COVID-19 FundraisingCampaign of Institut Pasteur. PB acknowledges funding from the Institut Pasteur and InsitutNational de la Santé et de la Recherche Médicale (INSERM). AS was supported by a Posted’accueil from INSERM.

Subjects
[SDV]Life Sciences [q-bio], [SDV.IMM]Life Sciences [q-bio]/Immunology
Abstract

SummaryHow infection by a viral variant showing antigenic drift impacts a preformed mature human memory B cell (MBC) repertoire remains an open question. Here, we studied the MBC response up to 6 months after Omicron BA.1 breakthrough infection in individuals previously vaccinated with three doses of mRNA vaccine. Longitudinal analysis, using single-cell multi-omics and functional analysis of monoclonal antibodies from RBD-specific MBCs, revealed that a BA.1 breakthrough infection mostly recruited pre-existing cross-reactive MBCs with limitedde novoresponse against BA.1-restricted epitopes. Reorganization of clonal hierarchy and new rounds of germinal center reaction, however, combined to maintain diversity and induce progressive maturation of the MBC repertoire against common Hu-1 and BA.1, but not BA.5-restricted, SARS-CoV-2 Spike RBD epitopes. Such remodeling was further associated with marked improvement in overall neutralizing breadth and potency. These findings have fundamental implications for the design of future vaccination booster strategies.

Published
2023

11. Seroepidemiology of the Seasonal Human Coronaviruses NL63, 229E, OC43 and HKU1 in France.

Author

Thoisy, Alix De, Woudenberg, Tom, Pelleau, Stéphane, Donnadieu, Françoise, Garcia, Laura, Pinaud, Laurie, Tondeur, Laura, Meola, Annalisa, Arowas, Laurence, Clement, Nathalie, Backovic, Marija, Ungeheuer, Marie-Noëlle, Fontanet, Arnaud, White, Michael, and teams, COVID-Oise and SeroPed study

Subjects
IMMUNOGLOBULIN G, CORONAVIRUSES, SEROCONVERSION, COHORT analysis, HUMAN beings
Abstract

Background The seasonal human coronaviruses (HCoV) NL63, 229E, OC43, and HKU1 are globally endemic, yet the majority of HCoV infections remain undiagnosed. Methods In a cross-sectional study, 2389 serum samples were collected from children and adults in France in 2020. In a longitudinal cohort study, 2520 samples were collected from 898 French individuals followed up between 2020 and 2021. Antibodies to HCoVs were measured using a bead-based multiplex assay. Results The rate of waning of anti-HCoV spike immunoglobulin G antibodies was estimated as 0.22–0.47 year−1 for children, and 0.13–0.27 year−1 for adults. Seroreversion was estimated as 0.31–1.37 year−1 in children and 0.19–0.72 year−1 in adults. The estimated seroconversion rate in children was consistent with 20%–39% of children being infected every year with each HCoV. Conclusions The high force of infection in children indicates that HCoVs may be responsible for a substantial proportion of fever episodes experienced by children. [ABSTRACT FROM AUTHOR]

Published
2023
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12. Microbial Protein Binding to gC1qR Drives PLA2G1B-Induced CD4 T-Cell Anergy

Author

Pothlichet, Julien, Meola, Annalisa, Bugault, Florence, Jeammet, Louise, Savitt, Anne, Ghebrehiwet, Berhane, Touqui, Lhousseine, Pouletty, Philippe, Fiore, Frédéric, Sauvanet, Alain, Thèze, Jacques, Diaccurate SAS, Stony Brook University [SUNY] (SBU), State University of New York (SUNY), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Mucoviscidose et bronchopathies chroniques : biopathologie et phénotype cliniques - Cystic Fibrosis and Bronchial Diseases, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [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)-Université Paris Cité (UPCité), Centre d'Immunophénomique (CIPHE), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de chirurgie hepato-pancreato-biliaire, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), This work was part of the ANRS program EP33., We are grateful to J.-F. Delfraissy and O. Lambotte that were principal investigators of the clinical study of HIV patients (the ANRS program EP33) and were involved in patient selection and the characterization of biological parameters. We thank G. Lambeau for helpful discussions and the gift of PLA2G1B proteins. We wish to thank E. Perret, P. Roux, A. Salles, and S. Shorte (UTechS PBI/C2RT, Institut Pasteur) for their microscopy expertise. We also wish to thank P. Casanova and S. Rosario (Service Prévention des Risques, Direction Ressources Techniques et Environnement, Institut Pasteur) for their help in the radioactivity platform. We are grateful to F. Rey, I. Fernandez, and P. Guardado Calvo for helpful discussions concerning the gp41 protein. We also thank B. Georges for the search for 3S-like peptide motifs in sequence databases. We gratefully acknowledge B. Malissen for his critical review of the manuscript., and Meola, Annalisa

Subjects
CD4-Positive T-Lymphocytes, staphylococcus aureus, PLA2G1B, infectious disease, [SDV]Life Sciences [q-bio], Immunology, MESH: Membrane Glycoproteins, HIV Infections, MESH: Carrier Proteins, porphyromonas gingivalis, Immunology and Allergy, Humans, MESH: Protein Binding, Group IB Phospholipases A2, MESH: Group IB Phospholipases A2, Clonal Anergy, Membrane Glycoproteins, MESH: Humans, Interleukin-7, HIV, MESH: CD4-Positive T-Lymphocytes, CD4 T cell, MESH: HIV Infections, MESH: Interleukin-7, Receptors, Complement, [SDV] Life Sciences [q-bio], MESH: Receptors, Complement, gC1qR, HCV, MESH: Clonal Anergy, Carrier Proteins, Protein Binding
Abstract

The origin of the impaired CD4 T-cell response and immunodeficiency of HIV-infected patients is still only partially understood. We recently demonstrated that PLA2G1B phospholipase synergizes with the HIV gp41 envelope protein in HIV viremic plasma to induce large abnormal membrane microdomains (aMMDs) that trap and inactivate physiological receptors, such as those for IL-7. However, the mechanism of regulation of PLA2G1B activity by the cofactor gp41 is not known. Here, we developed an assay to directly follow PLA2G1B enzymatic activity on CD4 T-cell membranes. We demonstrated that gp41 directly binds to PLA2G1B and increases PLA2G1B enzymatic activity on CD4 membrane. Furthermore, we show that the conserved 3S sequence of gp41, known to bind to the innate sensor gC1qR, increases PLA2G1B activity in a gC1qR-dependent manner using gC1qR KO cells. The critical role of the 3S motif and gC1qR in the inhibition of CD4 T-cell function by the PLA2G1B/cofactor system in HIV-infected patients led us to screen additional microbial proteins for 3S-like motifs and to study other proteins known to bind to the gC1qR to further investigate the role of the PLA2G1B/cofactor system in other infectious diseases and carcinogenesis. We have thus extended the PLA2G1B/cofactor system to HCV and Staphylococcus aureus infections and additional pathologies where microbial proteins with 3S-like motifs also increase PLA2G1B enzymatic activity. Notably, the bacteria Porphyromonas gingivalis, which is associated with pancreatic ductal adenocarcinoma (PDAC), encodes such a cofactor protein and increased PLA2G1B activity in PDAC patient plasma inhibits the CD4 response to IL-7. Our findings identify PLA2G1B/cofactor system as a CD4 T-cell inhibitor. It involves the gC1qR and disease-specific cofactors which are gC1qR-binding proteins that can contain 3S-like motifs. This mechanism involved in HIV-1 immunodeficiency could play a role in pancreatic cancer and several other diseases. These observations suggest that the PLA2G1B/cofactor system is a general CD4 T-cell inhibitor and pave the way for further studies to better understand the role of CD4 T-cell anergy in infectious diseases and tumor escape.

Published
2022

13. Analysis of mRNA vaccination-elicited RBD-specific memory B cells reveals strong but incomplete immune escape of the SARS-CoV-2 Omicron variant

Author

Sokal, Aurélien, primary, Broketa, Matteo, additional, Barba-Spaeth, Giovanna, additional, Meola, Annalisa, additional, Fernández, Ignacio, additional, Fourati, Slim, additional, Azzaoui, Imane, additional, de La Selle, Andrea, additional, Vandenberghe, Alexis, additional, Roeser, Anais, additional, Bouvier-Alias, Magali, additional, Crickx, Etienne, additional, Languille, Laetitia, additional, Michel, Marc, additional, Godeau, Bertrand, additional, Gallien, Sébastien, additional, Melica, Giovanna, additional, Nguyen, Yann, additional, Zarrouk, Virginie, additional, Canoui-Poitrine, Florence, additional, Noizat-Pirenne, France, additional, Megret, Jérôme, additional, Pawlotsky, Jean-Michel, additional, Fillatreau, Simon, additional, Simon-Lorière, Etienne, additional, Weill, Jean-Claude, additional, Reynaud, Claude-Agnès, additional, Rey, Félix A., additional, Bruhns, Pierre, additional, Chappert, Pascal, additional, and Mahévas, Matthieu, additional

Published
2022
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14. 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

15. Immune escape of SARS-CoV-2 Omicron variant from mRNA vaccination-elicited RBD-specific memory B cells.

Author

Sokal, Aurelien, primary, Broketa, Matteo, additional, Meola, Annalisa, additional, Barba-Spaeth, Giovanna, additional, Fernandez, Ignacio, additional, Fourati, Slim, additional, Azzaoui, Imane, additional, de La Selle, Andrea, additional, Vandenberghe, Alexis, additional, Roeser, Anais, additional, Bouvier-Alias, Magali, additional, Crickx, Etienne, additional, Languille, Laetitia, additional, Michel, Marc, additional, Godeau, Bertrand, additional, Gallien, Sebastien, additional, Melica, Giovanna, additional, Nguyen, Yann, additional, Zarrouk, Virginie, additional, Canoui-Poitrine, Florence, additional, Noizat-Pirenne, France, additional, Megret, Jerome, additional, Pawlotsky, Jean-Michel, additional, Fillatreau, Simon, additional, Simon-Loriere, Etienne, additional, Weill, Jean-Claude, additional, Reynaud, Claude-Agnes, additional, Rey, Felix A., additional, Bruhns, Pierre, additional, Chappert, Pascal, additional, and Mahevas, Matthieu, additional

Published
2021
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16. mRNA vaccination of naive and COVID-19-recovered individuals elicits potent memory B cells that recognize SARS-CoV-2 variants

Author

Sokal, Aurélien, primary, Barba-Spaeth, Giovanna, additional, Fernández, Ignacio, additional, Broketa, Matteo, additional, Azzaoui, Imane, additional, de La Selle, Andréa, additional, Vandenberghe, Alexis, additional, Fourati, Slim, additional, Roeser, Anais, additional, Meola, Annalisa, additional, Bouvier-Alias, Magali, additional, Crickx, Etienne, additional, Languille, Laetitia, additional, Michel, Marc, additional, Godeau, Bertrand, additional, Gallien, Sébastien, additional, Melica, Giovanna, additional, Nguyen, Yann, additional, Zarrouk, Virginie, additional, Canoui-Poitrine, Florence, additional, Pirenne, France, additional, Mégret, Jérôme, additional, Pawlotsky, Jean-Michel, additional, Fillatreau, Simon, additional, Bruhns, Pierre, additional, Rey, Felix A., additional, Weill, Jean-Claude, additional, Reynaud, Claude-Agnès, additional, Chappert, Pascal, additional, and Mahévas, Matthieu, additional

Published
2021
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17. La diversité du répertoire des cellules B mémoires fait face aux variants du SRAS-CoV2 après la vaccination par ARNm chez les individus naïfs et guéris

Author

Chappert, Pascal, primary, Sokal, Aurélien, additional, Barba-Spaeth, Giovanna, additional, Fernandez, Ignacio, additional, Broketta, Matteo, additional, Azzaoui, Imane, additional, De La Selle, Andrea, additional, Vandenberghe, Alexis, additional, Fourati, Slim, additional, Meola, Annalisa, additional, Bouvier-Alias, Magali, additional, Cricks, Etienne, additional, Languille, Laetitia, additional, Michel, Marc, additional, Godeau, Bertrand, additional, Canoui-Poitrine, Florence, additional, Pirenne, France, additional, Megret, Jérôme, additional, Pawlotsky, Jean-Michel, additional, Bruhns, Pierre, additional, Rey, Felix, additional, Weill, Jean-Claude, additional, Reynaud, Claude-Agnès, additional, and Mahévas, Matthieu, additional

Published
2021
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18. Kinetics of the SARS-CoV-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], 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]-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), Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Virologie Structurale - Structural Virology, Epidémiologie et modélisation de la résistance aux antimicrobiens - Epidemiology and modelling of bacterial escape to antimicrobials (EMAE), Institut Pasteur [Paris]-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 de Paris (UP), CIC Strasbourg (Centre d’Investigation Clinique Plurithématique (CIC - P) ), 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, 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]-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM), Direction de la recherche médicale de l'Institut Pasteur, Conservatoire National des Arts et Métiers [CNAM] (CNAM), The Walter and Eliza Hall Institute of Medical Research (WEHI), University of Melbourne, Vaccine Research Institute (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,SynarchiC, 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), HESAM Université (HESAM)-HESAM Université (HESAM)-Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université (HESAM)-HESAM Université (HESAM)-Institut Pasteur [Paris], and HESAM Université (HESAM)

Subjects
antibody kinetics, time since infection, sero-prevalence, surveillance, [SDV.IMM]Life Sciences [q-bio]/Immunology, SARS-SoV-2
Abstract

All data and code used for reproducing the results is freely available on GitHub: https://github.com/MWhite-InstitutPasteur/SARSCoV2_AB_kinetics.; International audience; 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 five 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 eleven 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 IgG remains, 31% (9%, 89%) anti-RBD IgG remains, and 7% (1%, 31%) 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 sero-prevalence 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.

Published
2021

19. Memory B cells control SARS-CoV-2 variants upon mRNA vaccination of naive and COVID-19 recovered individuals

Author

Sokal, Aurélien, primary, Barba-Spaeth, Giovanna, additional, Fernández, Ignacio, additional, Broketa, Matteo, additional, Azzaoui, Imane, additional, La Selle, Andrea de, additional, Vandenberghe, Alexis, additional, Fourati, Slim, additional, Roeser, Anais, additional, Meola, Annalisa, additional, Bouvier-Alias, Magali, additional, Crickx, Etienne, additional, Languille, Laetitia, additional, Michel, Marc, additional, Godeau, Bertrand, additional, Gallien, Sébastien, additional, Melica, Giovanna, additional, Nguyen, Yann, additional, Zarrouk, Virginie, additional, Canoui-Poitrine, Florence, additional, Noizat-Pirenne, France, additional, Megret, Jérôme, additional, Pawlotsky, Jean-Michel, additional, Fillatreau, Simon, additional, Bruhns, Pierre, additional, Rey, Felix A., additional, Weill, Jean-Claude, additional, Reynaud, Claude-Agnès, additional, Chappert, Pascal, additional, and Mahévas, Matthieu, additional

Published
2021
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20. Serological reconstruction of COVID-19 epidemics through analysis of antibody kinetics to SARS-CoV-2 proteins

Author

Pelleau, Stéphane, primary, Woudenberg, Tom, additional, Rosado, Jason, additional, Donnadieu, Françoise, additional, Garcia, Laura, additional, Obadia, Thomas, additional, Gardais, Soazic, additional, Elgharbawy, Yasmine, additional, Velay, Aurelie, additional, Gonzalez, Maria, additional, Nizou, Jacques Yves, additional, Khelil, Nizar, additional, Zannis, Konstantinos, additional, Cockram, Charlotte, additional, Hélène Merkling, Sarah, additional, Meola, Annalisa, additional, Kerneis, Solen, additional, Terrier, Benjamin, additional, de Seze, Jerome, additional, Planas, Delphine, additional, Schwartz, Olivier, additional, Dejardin, François, additional, Petres, Stéphane, additional, von Platen, Cassandre, additional, Arowas, Laurence, additional, de Facci, Louise Perrin, additional, Duffy, Darragh, additional, Cheallaigh, Clíona Ní, additional, Conlon, Niall, additional, Townsend, Liam, additional, Auerswald, Heidi, additional, Backovic, Marija, additional, Hoen, Bruno, additional, Fontanet, Arnaud, additional, Mueller, Ivo, additional, Fafi-Kremer, Samira, additional, Bruel, Timothée, additional, and White, Michael, additional

Published
2021
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21. Maturation and persistence of the anti-SARS-CoV-2 memory B cell response

Author

Sokal, Aurélien, primary, Chappert, Pascal, additional, Barba-Spaeth, Giovanna, additional, Roeser, Anais, additional, Fourati, Slim, additional, Azzaoui, Imane, additional, Vandenberghe, Alexis, additional, Fernandez, Ignacio, additional, Meola, Annalisa, additional, Bouvier-Alias, Magali, additional, Crickx, Etienne, additional, Beldi-Ferchiou, Asma, additional, Hue, Sophie, additional, Languille, Laetitia, additional, Michel, Marc, additional, Baloul, Samia, additional, Noizat-Pirenne, France, additional, Luka, Marine, additional, Mégret, Jérôme, additional, Ménager, Mickaël, additional, Pawlotsky, Jean-Michel, additional, Fillatreau, Simon, additional, Rey, Felix A., additional, Weill, Jean-Claude, additional, Reynaud, Claude-Agnès, additional, and Mahévas, Matthieu, additional

Published
2021
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22. Multiplex assays for the identification of serological signatures of SARS-CoV-2 infection: an antibody-based diagnostic and machine learning study

Author

Rosado, Jason, primary, Pelleau, Stéphane, additional, Cockram, Charlotte, additional, Merkling, Sarah Hélène, additional, Nekkab, Narimane, additional, Demeret, Caroline, additional, Meola, Annalisa, additional, Kerneis, Solen, additional, Terrier, Benjamin, additional, Fafi-Kremer, Samira, additional, de Seze, Jerome, additional, Bruel, Timothée, additional, Dejardin, François, additional, Petres, Stéphane, additional, Longley, Rhea, additional, Fontanet, Arnaud, additional, Backovic, Marija, additional, Mueller, Ivo, additional, and White, Michael T, additional

Published
2021
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26. Serological signatures of SARS-CoV-2 infection: Implications for antibody-based diagnostics

Author

Rosado, Jason, primary, Pelleau, Stéphane, additional, Cockram, Charlotte, additional, Hélène Merkling, Sarah, additional, Nekkab, Narimane, additional, Demeret, Caroline, additional, Meola, Annalisa, additional, Kerneis, Solen, additional, Terrier, Benjamin, additional, Fafi-Kremer, Samira, additional, de Seze, Jerome, additional, Dejardin, François, additional, Petres, Stéphane, additional, Longley, Rhea, additional, Backovic, Marija, additional, Mueller, Ivo, additional, and White, Michael T, additional

Published
2020
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28. The Ancient Gamete Fusogen HAP2 Is a Eukaryotic Class II Fusion Protein

Author

Fedry, Juliette, Liu, Yanjie, Pehau-Arnaudet, Gerard, Pei, Jimin, Li, Wenhao, Tortorici, M Alejandra, Traincard, François, Meola, Annalisa, Bricogne, Gérard, Grishin, Nick, Snell, William, Rey, Felix, Krey, Thomas, Virologie Structurale - Structural Virology, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Hannover Medical School [Hannover] (MHH), University of Texas Southwestern Medical Center, Microscopie ultrastructurale - Ultrapole (CITECH), Institut Pasteur [Paris] (IP), Ingénierie des Anticorps (plate-forme) - Antibody Engineering (Platform), Global Phasing Ltd, Global Phasing, German Center for Infection Research - partner site Hannover-Braunschweig (DZIF), F.A.R. acknowledges funding from the ERC Advanced grant project (340371) CelCelFus for this work, which also used general support from Institut Pasteur and CNRS. W.J.S. was supported by a grant from the NIH (GM56778) and acknowledges funding from the UTSW HI/HR Program. N.V.G. is funded, in part, by a grant from the NIH (GM094575) and the Welch Foundation (I-1505). J.F. benefitted from an Allocation ministérielle pour l'Ecole Polytechnique AMX., We thank Francis-André Wollmann and Sandrine Bujaldon for discussions and help with initial experiments, Fredrick Grinnell, Saikat Mukhopadhyay, Michael Henne, and Margaret Phillips of UT Southwestern for helpful discussions, the crystallization platform of the Pasteur Proteopole for technical help, Remi Fronzes for help with native PAGE experiments, Vincent Olieric and the staff of synchrotron beamlines PX-III at the Swiss Light Source, Proxima-1 and -2 at SOLEIL and ID29 and ID30-3 at the European Synchrotron Radiation Facility for help during data collection, members of the Rey and Snell labs for discussions, and M. Nilges and the Equipement d’excellence CACSICE for providing the Falcon II direct electron detector., European Project: 340371,EC:FP7:ERC,ERC-2013-ADG,CELCELFUS(2014), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), and Institut Pasteur [Paris]

Subjects
Plasmodium, crystal structure, transmission-blocking malaria vaccine, sexual reproduction, [SDV]Life Sciences [q-bio], membrane fusion, Protozoan Proteins, MESH: Sequence Alignment, MESH: Biological Evolution, MESH: Amino Acid Sequence, virus entry, Crystallography, X-Ray, gamete fusion, MESH: Chlamydomonas, Article, MESH: Recombinant Proteins, Protein Domains, lipid insertion, HAP2, Humans, Amino Acid Sequence, MESH: Membrane Fusion Proteins, MESH: Protozoan Proteins, Membrane Fusion Proteins, Plant Proteins, class II fusion protein, MESH: Plant Proteins, Biochemistry, Genetics and Molecular Biology(all), MESH: Plasmodium, Chlamydomonas, Eukaryota, MESH: Crystallography, X-Ray, Biological Evolution, Recombinant Proteins, MESH: Germ Cells, Germ Cells, Virus Diseases, MESH: Protein Domains, Sequence Alignment, Chlamydomonas reinhardtii
Abstract

Summary Sexual reproduction is almost universal in eukaryotic life and involves the fusion of male and female haploid gametes into a diploid cell. The sperm-restricted single-pass transmembrane protein HAP2-GCS1 has been postulated to function in membrane merger. Its presence in the major eukaryotic taxa—animals, plants, and protists (including important human pathogens like Plasmodium)—suggests that many eukaryotic organisms share a common gamete fusion mechanism. Here, we report combined bioinformatic, biochemical, mutational, and X-ray crystallographic studies on the unicellular alga Chlamydomonas reinhardtii HAP2 that reveal homology to class II viral membrane fusion proteins. We further show that targeting the segment corresponding to the fusion loop by mutagenesis or by antibodies blocks gamete fusion. These results demonstrate that HAP2 is the gamete fusogen and suggest a mechanism of action akin to viral fusion, indicating a way to block Plasmodium transmission and highlighting the impact of virus-cell genetic exchanges on the evolution of eukaryotic life., Graphical Abstract, Highlights • The primordial gamete fusogen HAP2 exhibits homology to class II viral fusion proteins • HAP2 inserts into the target gamete membrane via a hydrophobic fusion loop • HAP2 links virus entry into target cells and the origins of sexual reproduction • HAP2 is a sex-specific target for blocking fertilization in multiple kingdoms, Gamete fusion across eukaryotic branches uses an ancient factor homologous to viral fusion proteins.

Published
2017

29. Structural Snapshots of Eff-1 Mediated Membrane Fusion

Author

Dellarole, Mariano, primary, Meola, Annalisa, additional, Pehau-Arnaudet, Gérard, additional, Bontems, François, additional, Borgnia, Mario J., additional, Krey, Thomas, additional, Volkmann, Niels, additional, Hanein, Dorit, additional, and Rey, Félix A., additional

Published
2017
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31. Robust and low cost uniform 15N-labeling of proteins expressed in Drosophila S2 cells and Spodoptera frugiperda Sf9 cells for NMR applications

Author

Meola, Annalisa, primary, Deville, Célia, additional, Jeffers, Scott A., additional, Guardado-Calvo, Pablo, additional, Vasiliauskaite, Ieva, additional, Sizun, Christina, additional, Girard-Blanc, Christine, additional, Malosse, Christian, additional, van Heijenoort, Carine, additional, Chamot-Rooke, Julia, additional, Krey, Thomas, additional, Guittet, Eric, additional, Pêtres, Stéphane, additional, Rey, Félix A., additional, and Bontems, François, additional

Published
2014
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34. Vaccine Vectors Derived from a Large Collection of Simian Adenoviruses Induce Potent Cellular Immunity Across Multiple Species

Author

Colloca, Stefano, primary, Barnes, Eleanor, additional, Folgori, Antonella, additional, Ammendola, Virginia, additional, Capone, Stefania, additional, Cirillo, Agostino, additional, Siani, Loredana, additional, Naddeo, Mariarosaria, additional, Grazioli, Fabiana, additional, Esposito, Maria Luisa, additional, Ambrosio, Maria, additional, Sparacino, Angela, additional, Bartiromo, Marta, additional, Meola, Annalisa, additional, Smith, Kira, additional, Kurioka, Ayako, additional, O’Hara, Geraldine A., additional, Ewer, Katie J., additional, Anagnostou, Nicholas, additional, Bliss, Carly, additional, Hill, Adrian V. S., additional, Traboni, Cinzia, additional, Klenerman, Paul, additional, Cortese, Riccardo, additional, and Nicosia, Alfredo, additional

Published
2012
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35. Isolation of Fully Human Antagonistic RON Antibodies Showing Efficient Block of Downstream Signaling and Cell Migration

Author

Gunes, Zeynep, primary, Zucconi, Adriana, additional, Cioce, Mario, additional, Meola, Annalisa, additional, Pezzanera, Monica, additional, Acali, Stefano, additional, Zampaglione, Immacolata, additional, De Pratti, Valeria, additional, Bova, Luca, additional, Talamo, Fabio, additional, Demartis, Anna, additional, Monaci, Paolo, additional, La Monica, Nicola, additional, Ciliberto, Gennaro, additional, and Vitelli, Alessandra, additional

Published
2011
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36. Anti-EphA2 Antibodies with Distinct In Vitro Properties Have Equal In Vivo Efficacy in Pancreatic Cancer

Author

Ansuini, Helenia, primary, Meola, Annalisa, additional, Gunes, Zeynep, additional, Paradisi, Valentina, additional, Pezzanera, Monica, additional, Acali, Stefano, additional, Santini, Claudia, additional, Luzzago, Alessandra, additional, Mori, Federica, additional, Lazzaro, Domenico, additional, Ciliberto, Gennaro, additional, Nicosia, Alfredo, additional, La Monica, Nicola, additional, and Vitelli, Alessandra, additional

Published
2009
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37. Modulation of the Immune Response Induced by Gene Electrotransfer of a Hepatitis C Virus DNA Vaccine in Nonhuman Primates

Author

Capone, Stefania, primary, Zampaglione, Immacolata, additional, Vitelli, Alessandra, additional, Pezzanera, Monica, additional, Kierstead, Lisa, additional, Burns, Janine, additional, Ruggeri, Lionello, additional, Arcuri, Mirko, additional, Cappelletti, Manuela, additional, Meola, Annalisa, additional, Ercole, Bruno Bruni, additional, Tafi, Rosalba, additional, Santini, Claudia, additional, Luzzago, Alessandra, additional, Fu, Tong-Ming, additional, Colloca, Stefano, additional, Ciliberto, Gennaro, additional, Cortese, Riccardo, additional, Nicosia, Alfredo, additional, Fattori, Elena, additional, and Folgori, Antonella, additional

Published
2006
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38. A Novel Adenovirus Type 6 (Ad6)-Based Hepatitis C Virus Vector That Overcomes Preexisting Anti-Ad5 Immunity and Induces Potent and Broad Cellular Immune Responses in Rhesus Macaques

Author

Capone, Stefania, primary, Meola, Annalisa, additional, Ercole, Bruno Bruni, additional, Vitelli, Alessandra, additional, Pezzanera, Monica, additional, Ruggeri, Lionello, additional, Davies, Mary Ellen, additional, Tafi, Rosalba, additional, Santini, Claudia, additional, Luzzago, Alessandra, additional, Fu, Tong-Ming, additional, Bett, Andrew, additional, Colloca, Stefano, additional, Cortese, Riccardo, additional, Nicosia, Alfredo, additional, and Folgori, Antonella, additional

Published
2006
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39. Binding of the Hepatitis C Virus E2 Glycoprotein to CD81 Is Strain Specific and Is Modulated by a Complex Interplay between Hypervariable Regions 1 and 2

Author

Roccasecca, RosaMaria, primary, Ansuini, Helenia, additional, Vitelli, Alessandra, additional, Meola, Annalisa, additional, Scarselli, Elisa, additional, Acali, Stefano, additional, Pezzanera, Monica, additional, Ercole, Bruno Bruni, additional, McKeating, Jane, additional, Yagnik, Asutosh, additional, Lahm, Armin, additional, Tramontano, Anna, additional, Cortese, Riccardo, additional, and Nicosia, Alfredo, additional

Published
2003
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42. Induction of Cross-reactive Humoral Immune Response by Immunization with Mimotopes of the Hypervariable Region 1 of the Hepatitis C Virus

Author

Roccasecca, Rosamaria, primary, Folgori, Antonella, additional, Ercole, Bruno Bruni, additional, Puntoriero, Giulia, additional, Lahm, Armin, additional, Zucchelli, Silvia, additional, Tafi, Rosalba, additional, Pezzanera, Monica, additional, Galfre, Giovanni, additional, Tramontano, Anna, additional, Mondelli, M. U., additional, Pessi, Antonello, additional, Nicosia, Alfredo, additional, Cortese, Riccardo, additional, and Meola, Annalisa, additional

Published
2001
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43. Binding of Hepatitis C Virus E2 Glycoprotein to CD81 Does Not Correlate with Species Permissiveness to Infection

Author

Meola, Annalisa, primary, Sbardellati, Andrea, additional, Bruni Ercole, Bruno, additional, Cerretani, Mauro, additional, Pezzanera, Monica, additional, Ceccacci, Alessandra, additional, Vitelli, Alessandra, additional, Levy, Shoshana, additional, Nicosia, Alfredo, additional, Traboni, Cinzia, additional, McKeating, Jane, additional, and Scarselli, Elisa, additional

Published
2000
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45. Antibody responses to hepatitis C virus hypervariable region 1: Evidence for cross-reactivity and immune-mediated sequence variation

Author

Mondelli, Mario U., primary, Cerino, Antonella, additional, Lisa, Antonella, additional, Brambilla, Sabrina, additional, Segagni, Laura, additional, Cividini, Agostino, additional, Bissolati, Morena, additional, Missale, Gabriele, additional, Bellati, Giorgio, additional, Meola, Annalisa, additional, Bruniercole, Bruno, additional, Nicosia, Alfredo, additional, Galfrè, Giovanni, additional, and Silini, Enrico, additional

Published
1999
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48. Towards a solution for hepatitis C virus hypervariability: mimotopes of the hypervariable region 1 can induce antibodies cross-reacting with a large number of viral variants.

Author

Puntoriero, Giulia, Meola, Annalisa, Lahm, Armin, Zucchelli, Silvia, Ercole, Bruno Bruni, Tafi, Rosalba, Pezzanera, Monica, Mondelli, Mario U., Cortese, Riccardo, Tramontano, Anna, Galfre, Giovanni, and Nicosia, Alfredo

Subjects
*PROTEINS, *HEPATITIS C virus, *ANTIGENS, *VIRAL genomes, *HETEROGENEITY, *VIRUS diseases, *IMMUNE response, *IMMUNOGLOBULINS
Abstract

The hypervariable region 1 (HVR1) of the putative envelope protein E2 of hepatitis C virus (HCV) is the most variable antigenic fragment in the whole viral genome and is mainly responsible for the large inter- and intra-individual heterogeneity of the infecting virus. It contains a principal neutralization epitope and has been proposed as the major player in the mechanism of escape from host immune response. Since anti-HVR1 antibodies are the only species shown to possess protective activity up to date, developing an effective prevention therapy is a very difficult task. We have approached the problem of HVR1 variability by deriving a consensus profile from >200 HVR1 sequences from different viral isolates and used it as a template to generate a vast repertoire of synthetic HVR1 surrogates displayed on M13 bacteriophage. This library was affinity selected using many different sera from infected patients. Phages were identified which react very frequently with patients' sera and bind serum antibodies that cross-react with a large panel of HVR1 peptides derived from natural HCV variants. When injected into experimental animals, the ‘mimotopes’ with the highest cross-reactivity induced antibodies which recognized the same panel of natural HVR1 variants. In these mimotopes we identified a sequence pattern responsible for the observed cross-reactivity. These data may hold the key for future development of a prophylactic vaccine against HCV. [ABSTRACT FROM AUTHOR]

Published
1998
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49. Production and Purification of Hantavirus Glycoproteins in Drosophila melanogaster S2 Cells.

Author

Meola A and Guardado-Calvo P

Subjects
Humans, Animals, Drosophila melanogaster metabolism, Viral Envelope Proteins genetics, Viral Envelope Proteins metabolism, Glycoproteins metabolism, Orthohantavirus, RNA Viruses
Abstract

Hantaviruses, are rodent-borne viruses found worldwide that are transmitted to humans through inhalation of contaminated excreta. They can cause a renal or a pulmonary syndrome, depending on the virus, and no effective treatment is currently available for either of these diseases. Hantaviral particles are covered by a protein lattice composed of two glycoproteins (Gn and Gc) that mediate adsorption to target cells and fusion with endosomal membranes, making them prime targets for neutralizing antibodies. Here we present the methodology to produce soluble recombinant glycoproteins in different conformations, either alone or as a stabilized Gn/Gc complex, using stably transfected Drosophila S2 cells., (© 2024. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Published
2024
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50. Seroepidemiology of the Seasonal Human Coronaviruses NL63, 229E, OC43 and HKU1 in France.

Author

De Thoisy A, Woudenberg T, Pelleau S, Donnadieu F, Garcia L, Pinaud L, Tondeur L, Meola A, Arowas L, Clement N, Backovic M, Ungeheuer MN, Fontanet A, and White M

Abstract

Background: The seasonal human coronaviruses (HCoV) NL63, 229E, OC43, and HKU1 are globally endemic, yet the majority of HCoV infections remain undiagnosed., Methods: In a cross-sectional study, 2389 serum samples were collected from children and adults in France in 2020. In a longitudinal cohort study, 2520 samples were collected from 898 French individuals followed up between 2020 and 2021. Antibodies to HCoVs were measured using a bead-based multiplex assay., Results: The rate of waning of anti-HCoV spike immunoglobulin G antibodies was estimated as 0.22-0.47 year -1 for children, and 0.13-0.27 year -1 for adults. Seroreversion was estimated as 0.31-1.37 year -1 in children and 0.19-0.72 year -1 in adults. The estimated seroconversion rate in children was consistent with 20%-39% of children being infected every year with each HCoV., Conclusions: The high force of infection in children indicates that HCoVs may be responsible for a substantial proportion of fever episodes experienced by children., Competing Interests: Potential conflicts of interest. All authors report that they have no conflicts of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Published
2023
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