Author: "Vanessa Contreras" / Topic: medicine - Searchworks@Jio Institute Digital Library Search Results

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1. Immunogenicity and efficacy of VLA2001 vaccine against SARS-CoV-2 infection in male cynomolgus macaques

Author: Mathilde Galhaut, Urban Lundberg, Romain Marlin, Robert Schlegl, Stefan Seidel, Ursula Bartuschka, Jürgen Heindl-Wruss, Francis Relouzat, Sébastien Langlois, Nathalie Dereuddre-Bosquet, Julie Morin, Maxence Galpin-Lebreau, Anne-Sophie Gallouët, Wesley Gros, Thibaut Naninck, Quentin Pascal, Catherine Chapon, Karine Mouchain, Guillaume Fichet, Julien Lemaitre, Mariangela Cavarelli, Vanessa Contreras, Nicolas Legrand, Andreas Meinke, and Roger Le Grand
Subjects: Medicine
Abstract: Abstract Background The fight against COVID-19 requires mass vaccination strategies, and vaccines inducing durable cross-protective responses are still needed. Inactivated vaccines have proven lasting efficacy against many pathogens and good safety records. They contain multiple protein antigens that may improve response breadth and can be easily adapted every year to maintain preparedness for future seasonally emerging variants. Methods The vaccine dose was determined using ELISA and pseudoviral particle-based neutralization assay in the mice. The immunogenicity was assessed in the non-human primates with multiplex ELISA, neutralization assays, ELISpot and intracellular staining. The efficacy was demonstrated by viral quantification in fluids using RT-qPCR and respiratory tissue lesions evaluation. Results Here we report the immunogenicity and efficacy of VLA2001 in animal models. VLA2001 formulated with alum and the TLR9 agonist CpG 1018™ adjuvant generate a Th1-biased immune response and serum neutralizing antibodies in female BALB/c mice. In male cynomolgus macaques, two injections of VLA2001 are sufficient to induce specific and polyfunctional CD4+ T cell responses, predominantly Th1-biased, and high levels of antibodies neutralizing SARS-CoV-2 infection in cell culture. These antibodies also inhibit the binding of the Spike protein to human ACE2 receptor of several variants of concern most resistant to neutralization. After exposure to a high dose of homologous SARS-CoV-2, vaccinated groups exhibit significant levels of protection from viral replication in the upper and lower respiratory tracts and from lung tissue inflammation. Conclusions We demonstrate that the VLA2001 adjuvanted vaccine is immunogenic both in mouse and NHP models and prevent cynomolgus macaques from the viruses responsible of COVID-19.
Published: 2024
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2. Intradermal vaccination prevents anti-MOG autoimmune encephalomyelitis in macaquesResearch in context

Author: Claire-Maëlle Fovet, Lev Stimmer, Vanessa Contreras, Philippe Horellou, Audrey Hubert, Nabila Seddiki, Catherine Chapon, Sabine Tricot, Carole Leroy, Julien Flament, Julie Massonneau, Nicolas Tchitchek, Bert A. 't Hart, Sandra Zurawski, Peter Klucar, Philippe Hantraye, Kumaran Deiva, Gerard Zurawski, SangKon Oh, Roger Le Grand, and Ché Serguera
Subjects: Medicine, Medicine (General), R5-920
Abstract: Background: Autoimmune demyelinating diseases (ADD) are a major cause of neurological disability due to autoreactive cellular and humoral immune responses against brain antigens. A cure for chronic ADD could be obtained by appropriate immunomodulation. Methods: We implemented a preclinical scheme to foster immune tolerance to myelin oligodendrocyte glycoprotein (MOG), in a cynomolgus-macaque model of experimental autoimmune encephalomyelitis (EAE), in which administration of recombinant human MOG (rhMOG) elicits brain inflammation mediated by MOG-autoreactive CD4+ lymphocytes and anti-MOG IgG. For immunotherapy, we used a recombinant antibody (Ab) directed against the dendritic cell-asialoglycoprotein receptor (DC-ASGPR) fused either to MOG or a control antigen PSA (prostate-specific antigen). Findings: rhMOG and the anti-DC-ASGPR-MOG were respectively detected in CD1a+ DCs or CD163+ cells in the skin of macaques. Intradermal administration of anti-DC-ASGPR-MOG, but not control anti-DC-ASGPR-PSA, was protective against EAE. The treatment prevented the CD4+ T cell activation and proinflammatory cytokine production observed in controls. Moreover, the administration of anti-DC-ASGPR-MOG induced MOG-specific CD4+CD25+FOXP3+CD39+ regulatory lymphocytes and favoured an upsurge in systemic TGFβ and IL-8 upon rhMOG re-administration in vivo. Interpretation: We show that the delivery of an anti-DC-ASGPR-MOG allows antigen-specific adaptive immune modulation to prevent the breach of immune tolerance to MOG. Our findings pave the way for therapeutic vaccines for long-lasting remission to grave encephalomyelitis with identified autoantigens, such as ADD associated with anti-MOG autoantibodies. Fund: Work supported by the French ANR (ANR-11-INBS-0008 and ANR-10-EQPX-02-01), NIH (NIH 1 R01 AI 105066), the Baylor Scott and White Healthcare System funding and Roche Research Collaborative grants. Keywords: EAE, TGFβ, Tolerance, Treg, Anti-MOG IgG, Macaque
Published: 2019
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3. Delivering HIV Gagp24 to DCIR Induces Strong Antibody Responses In Vivo.

Author: Anne-Laure Flamar, Vanessa Contreras, Sandra Zurawski, Monica Montes, Nathatlie Dereuddre-Bosquet, Frédéric Martinon, Jacques Banchereau, Roger Le Grand, Gerard Zurawski, and Yves Levy
Subjects: Medicine, Science
Abstract: Targeting dendritic cell-specific endocytic receptors using monoclonal antibodies fused to desired antigens is an approach widely used in vaccine development to enhance the poor immunogenicity of protein-based vaccines and to induce immune responses. Here, we engineered an anti-human DCIR recombinant antibody, which cross-reacts with the homologous cynomolgous macaque receptor and was fused via the heavy chain C-terminus to HIV Gagp24 protein (αDCIR.Gagp24). In vitro, αDCIR.Gagp24 expanded multifunctional antigen-specific memory CD4+ T cells recognizing multiple Gagp24 peptides from HIV-infected patient peripheral blood mononuclear cells. In non human primates, priming with αDCIR.Gagp24 without adjuvant elicited a strong anti-Gagp24 antibody response after the second immunization, while in the non-targeted HIV Gagp24 protein control groups the titers were weak. The presence of the double-stranded RNA poly(I:C) adjuvant significantly enhanced the anti-Gagp24 antibody response in all the groups and reduced the discrimination between the different vaccine groups. The avidity of the anti-Gagp24 antibody responses was similar with either αDCIR.Gagp24 or Gagp24 immunization, but increased from medium to high avidity in both groups when poly(I:C) was co-administered. This data provides a comparative analysis of DC-targeted and non-targeted proteins for their capacity to induce antigen-specific antibody responses in vivo. This study supports the further development of DCIR-based DC-targeting vaccines for protective durable antibody induction, especially in the absence of adjuvant.
Published: 2015
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4. Expression of VP7, a Bluetongue virus group specific antigen by viral vectors: analysis of the induced immune responses and evaluation of protective potential in sheep.

Author: Coraline Bouet-Cararo, Vanessa Contreras, Agathe Caruso, Sokunthea Top, Marion Szelechowski, Corinne Bergeron, Cyril Viarouge, Alexandra Desprat, Anthony Relmy, Jean-Michel Guibert, Eric Dubois, Richard Thiery, Emmanuel Bréard, Stephane Bertagnoli, Jennifer Richardson, Gilles Foucras, Gilles Meyer, Isabelle Schwartz-Cornil, Stephan Zientara, and Bernard Klonjkowski
Subjects: Medicine, Science
Abstract: Bluetongue virus (BTV) is an economically important Orbivirus transmitted by biting midges to domestic and wild ruminants. The need for new vaccines has been highlighted by the occurrence of repeated outbreaks caused by different BTV serotypes since 1998. The major group-reactive antigen of BTV, VP7, is conserved in the 26 serotypes described so far, and its role in the induction of protective immunity has been proposed. Viral-based vectors as antigen delivery systems display considerable promise as veterinary vaccine candidates. In this paper we have evaluated the capacity of the BTV-2 serotype VP7 core protein expressed by either a non-replicative canine adenovirus type 2 (Cav-VP7 R0) or a leporipoxvirus (SG33-VP7), to induce immune responses in sheep. Humoral responses were elicited against VP7 in almost all animals that received the recombinant vectors. Both Cav-VP7 R0 and SG33-VP7 stimulated an antigen-specific CD4+ response and Cav-VP7 R0 stimulated substantial proliferation of antigen-specific CD8+ lymphocytes. Encouraged by the results obtained with the Cav-VP7 R0 vaccine vector, immunized animals were challenged with either the homologous BTV-2 or the heterologous BTV-8 serotype and viral burden in plasma was followed by real-time RT-PCR. The immune responses triggered by Cav-VP7 R0 were insufficient to afford protective immunity against BTV infection, despite partial protection obtained against homologous challenge. This work underscores the need to further characterize the role of BTV proteins in cross-protective immunity.
Published: 2014
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5. Canine recombinant adenovirus vector induces an immunogenicity-related gene expression profile in skin-migrated CD11b⁺ -type DCs.

Author: Vanessa Contreras, Céline Urien, Luc Jouneau, Mickael Bourge, Coraline Bouet-Cararo, Michel Bonneau, Stephan Zientara, Bernard Klonjkowski, and Isabelle Schwartz-Cornil
Subjects: Medicine, Science
Abstract: Gene expression profiling of the blood cell response induced early after vaccination has previously been demonstrated to predict the immunogenicity of vaccines. In this study, we evaluated whether the analysis of the gene expression profile of skin-migrated dendritic cells (DCs) could be informative for the in vitro prediction of immunogenicity of vaccine, using canine adenovirus serotype 2 (CAV2) as vaccine vector. CAV2 has been shown to induce immunity to transgenes in several species including sheep and is an interesting alternative to human adenovirus-based vectors, based on the safety records of the parental strain in dogs and the lack of pre-existing immunity in non-host species. Skin-migrated DCs were collected from pseudo-afferent lymph in sheep. Both the CD11b(+) -type and CD103(+) -type skin-migrated DCs were transduced by CAV2. An analysis of the global gene response to CAV2 in the two skin DC subsets showed that the gene response in CD11b(+) -type DCs was far higher and broader than in the CD103(+) -type DCs. A newly released integrative analytic tool from Ingenuity systems revealed that the CAV2-modulated genes in the CD11b(+) -type DCs clustered in several activated immunogenicity-related functions, such as immune response, immune cell trafficking and inflammation. Thus gene profiling in skin-migrated DC in vitro indicates that the CD11b(+) DC type is more responsive to CAV2 than the CD103(+) DC type, and provides valuable information to help in evaluating and possibly improving viral vector vaccine effectiveness.
Published: 2012
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6. Immunization with synthetic SARS-CoV-2 S glycoprotein virus-like particles protects macaques from infection

Author: Isabelle Bally, Judith A. Burger, Rogier W. Sanders, M. Buisson, Wesley Gros, Pascal Poignard, Axelle Amen, Roger Le Grand, Daphna Fenel, Francis Relouzat, Guy Schoehn, Camille Bouillier, Vanessa Contreras, Nicole M. Thielens, Julien Lemaitre, Franck Fieschi, Guidenn Sulbaran, Sylvie van der Werf, Anne-Sophie Gallouet, Nathalie Dereuddre-Bosquet, Winfried Weissenhorn, Romain Marlin, Michel Thépaut, Thibaut Naninck, Delphine Guilligay, Sebastian Dergan Dylon, Marit J. van Gils, Pauline Maisonnasse, Meliawati Poniman, Institut de biologie structurale (IBS - UMR 5075), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), 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)-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)-Université Grenoble Alpes (UGA), 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, Department of Medical Microbiology and Infection Prevention [Amsterdam], University of Amsterdam [Amsterdam] (UvA), 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), Centre National de Référence des virus des infections respiratoires (dont la grippe) - National Reference Center Virus Influenzae [Paris] (CNR), Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), This work acknowledges support by the European Union's Horizon 2020 research and innovation program under grant agreement no. 681032, H2020 EHVA (W.W.), the ANR, RA-Covid-19 (W.W. and R.l.G.), and the CNRS (W.W.). W.W. acknowledges access to the platforms of the Grenoble Instruct-ERIC center (IBS and ISBG, UMS 3518 CNRS-CEA-UGA-EMBL) within the Grenoble Partnership for Structural Biology (PSB), with support from FRISBI (ANR-10-INBS-05-02) and GRAL, a project of the University Grenoble Alpes graduate school (Ecoles Universitaires de Recherche) CBH-EUR-GS (ANR-17-EURE-0003). The IBS acknowledges integration into the Interdisciplinary Research Institute of Grenoble (IRIG, CEA) and financial support from CEA, CNRS, and UGA. The Infectious Disease Models and Innovative Therapies (IDMIT) research infrastructure is supported by the Program Investissements d’Avenir, managed by the National Research Agency (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 Médicale (AM-CoV-Path), and the European Infrastructure TRANSVAC2 (730964). We acknowledge support from CoVIC, supported by the Bill and Melinda Gates Foundation. The virus stock was obtained through the EVAg platform (https://www.european-virus-archive.com/), funded by H2020 (653316)., ANR-10-INBS-0005,FRISBI,Infrastructure Française pour la Biologie Structurale Intégrée(2010), ANR-17-EURE-0003,CBH-EUR-GS,CBH-EUR-GS(2017), ANR-11-INBS-0008,IDMIT,Infrastructure nationale pour la modélisation des maladies infectieuses humaines(2011), European Project: 681032,H2020,H2020-PHC-2015-single-stage_RTD,EHVA(2016), European Project: 730964, H2020, RIA,H2020-INFRAIA-2016-1,TRANSVAC2(2017), European Project: 653316,H2020,H2020-INFRAIA-2014-2015,EVAg(2015), Thomas, Frank, Infrastructure Française pour la Biologie Structurale Intégrée - - FRISBI2010 - ANR-10-INBS-0005 - INBS - VALID, CBH-EUR-GS - - CBH-EUR-GS2017 - ANR-17-EURE-0003 - EURE - VALID, Infrastructures - Infrastructure nationale pour la modélisation des maladies infectieuses humaines - - IDMIT2011 - ANR-11-INBS-0008 - INBS - VALID, European HIV Vaccine Alliance (EHVA): a EU platform for the discovery and evaluation of novel prophylactic and therapeutic vaccine candidates - EHVA - - H20202016-01-01 - 2020-12-31 - 681032 - VALID, European Vaccine Research and Development Infrastructure - TRANSVAC2 - - H2020, RIA2017-05-01 - 2022-04-30 - 730964 - VALID, European Virus Archive goes global - EVAg - - H20202015-04-01 - 2019-03-31 - 653316 - VALID, Medical Microbiology and Infection Prevention, AII - Infectious diseases, Graduate School, Centre National de Référence des virus des infections respiratoires (dont la grippe) - National Reference Center Virus Influenzae [Paris] (CNR - laboratoire coordonnateur), Epidémiologie et Physiopathologie des Virus Oncogènes / Oncogenic Virus Epidemiology and Pathophysiology (EPVO (UMR_3569 / U-Pasteur_3)), platforms of the Grenoble Instruct-ERIC center (IBS and ISBG, and UMS 3518 CNRS-CEA-UGA-EMBL)
Subjects: Male, [SDV]Life Sciences [q-bio], MESH: Spike Glycoprotein, Coronavirus, Antibodies, Viral, Neutralization, MESH: Antibodies, Neutralizing, MESH: Chlorocebus aethiops, Chlorocebus aethiops, MESH: COVID-19, antibodies, MESH: Animals, MESH: Treatment Outcome, MESH: Immunoglobulin G, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Vaccination, Antibody titer, formaldehyde cross-linking, protection, S glycoprotein, medicine.anatomical_structure, Treatment Outcome, MESH: COVID-19 Vaccines, MESH: HEK293 Cells, Spike Glycoprotein, Coronavirus, Antibody, MESH: Pandemics, COVID-19 Vaccines, [SDV.BBM.BS] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], macaques, T cell, MESH: Vero Cells, Biology, General Biochemistry, Genetics and Molecular Biology, Virus, Article, Immunity, medicine, Animals, Humans, MESH: SARS-CoV-2, Vaccines, Virus-Like Particle, MESH: Immunoglobulin A, MESH: Vaccines, Virus-Like Particle, Pandemics, Vero Cells, B cells, MESH: Humans, SARS-CoV-2, COVID-19, MESH: Vaccination, Th1 Cells, Virology, Antibodies, Neutralizing, immunity, MESH: Male, Immunoglobulin A, Disease Models, Animal, Macaca fascicularis, HEK293 Cells, Immunization, MESH: Macaca fascicularis, MESH: Th1 Cells, Immunoglobulin G, Liposomes, biology.protein, MESH: Liposomes, nanoparticles, MESH: Disease Models, Animal, MESH: Antibodies, Viral
Abstract: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has caused an ongoing global health crisis. Here, we present as a vaccine candidate synthetic SARS-CoV-2 spike (S) glycoprotein-coated lipid vesicles that resemble virus-like particles. Soluble S glycoprotein trimer stabilization by formaldehyde cross-linking introduces two major inter-protomer cross-links that keep all receptor-binding domains in the “down” conformation. Immunization of cynomolgus macaques with S coated onto lipid vesicles (S-LVs) induces high antibody titers with potent neutralizing activity against the vaccine strain, Alpha, Beta, and Gamma variants as well as T helper (Th)1 CD4+-biased T cell responses. Although anti-receptor-binding domain (RBD)-specific antibody responses are initially predominant, the third immunization boosts significant non-RBD antibody titers. Challenging vaccinated animals with SARS-CoV-2 shows a complete protection through sterilizing immunity, which correlates with the presence of nasopharyngeal anti-S immunoglobulin G (IgG) and IgA titers. Thus, the S-LV approach is an efficient and safe vaccine candidate based on a proven classical approach for further development and clinical testing., Graphical abstract, Sulbaran et al. find that formaldehyde cross-linked S lipid nanoparticles induce potent neutralizing antibody titers upon cynomolgus macaque vaccination. Notably, vaccinated animals develop sterilizing immunity as highlighted upon virus challenge. Thus, the study provides a path to induce sterilizing immunity correlating with mucosal immune responses, which are desired to prevent virus spreading.
Published: 2022

7. 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

8. NK cell spatial dynamics and IgA responses in gut-associated lymphoid tissues during SIV infections

Author: Michaela Müller-Trutwin, Philippe Rascle, Hugo Mouquet, Vanessa Contreras, Marie Lazzerini, Nicolas Huot, Asier Sáez-Cirión, Caroline Passaes, Cyril Planchais, Beatrice Jacquelin, Université Paris Diderot, Sorbonne Paris Cité, Paris, France, Université Paris Diderot - Paris 7 (UPD7), HIV, Inflammation et persistance - HIV, Inflammation and Persistence, 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), Immunologie des Maladies Virales et Autoimmunes (IMVA - U1184), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), NH was supported by the Fondation J. Beytout and Institut Pasteur. PR was recipient of a PhD fellowship from the University Paris Diderot, Sorbonne Paris Cité and supported by the NIH (R01AI143457) and Institut Pasteur. CaP was recipient of a Roux-Cantarini Postdoctoral Fellowship. Cy.P. was the recipient of an ANRS post-doctoral fellowship. We would like to acknowledge grant support from Sidaction and ANRS to MMT. H.M. received core grants from the Institut Pasteur, the INSERM and the Milieu Intérieur Program (ANR-10-LABX-69-01) and was supported by an ANRS grant. We gratefully acknowledge the support to IDMIT from the French government: Investments for the Future program for infrastructures (PIA) through the ANR-11-INBS-0008 grant as well as from the PIA grant ANR-10-EQPX-02-01 to the FlowCyTech facility at IDMIT. We equally acknowledge the Investments for Future grant ANR-10–INSB–04 to support the UtechS Photonic BioImaging (Imagopole) and C2RT facilities at Institut Pasteur., ANR-10-LABX-0069,MILIEU INTERIEUR,GENETIC & ENVIRONMENTAL CONTROL OF IMMUNE PHENOTYPE VARIANCE: ESTABLISHING A PATH TOWARDS PERSONALIZED MEDICINE(2010), ANR-11-INBS-0008,IDMIT,Infrastructure nationale pour la modélisation des maladies infectieuses humaines(2011), ANR-10-EQPX-0002,FlowCyTech,Plateforme de phénotypage en Mass cytométrie pour l'analyse multiparamétrique de biomarqueurs complexes de l'efficacité de nouvelles stratégies thérapeutiques ou vaccinales(2010), and ANR-10-INBS-0004,France-BioImaging,Développment d'une infrastructure française distribuée coordonnée(2010)
Subjects: MESH: Killer Cells, Natural, [SDV]Life Sciences [q-bio], animal diseases, MESH: Simian Immunodeficiency Virus, Cell, Medicine (miscellaneous), HIV Infections, MESH: Lymph Nodes, Biology, General Biochemistry, Genetics and Molecular Biology, Text mining, MESH: Chlorocebus aethiops, Chlorocebus aethiops, medicine, Animals, MESH: Animals, MESH: Immunoglobulin A, Intestinal Mucosa, business.industry, Dynamics (mechanics), MESH: HIV Infections, Immunoglobulin A, Killer Cells, Natural, medicine.anatomical_structure, Immunology, MESH: Intestinal Mucosa, Simian Immunodeficiency Virus, Lymph Nodes, General Agricultural and Biological Sciences, business
Abstract: HIV infection induces tissue damage including lymph node (LN) fibrosis and intestinal epithelial barrier disruption leading to bacterial translocation and systemic inflammation. Natural hosts of SIV, such as African Green Monkeys (AGM), do not display tissue damage despite high viral load in blood and intestinal mucosa. AGM mount a NK cell-mediated control of SIVagm replication in peripheral LN. We analyzed if NK cells also control SIVagm in mesenteric (mes) LN and if this has an impact on gut humoral responses, in particular on the production of IgA known for their anti-inflammatory role in the gut. We show that NK cells migrate into and control viral replication in B cell follicles (BCF) of mesLN during SIVagm infection. IgA+ memory B cells were increased in mesLN during SIVagm infection in contrast to SIVmac infection and correlated positively with CXCR5+ NK cell levels. Total IgA levels in gut remained normal during SIVagm infection, while strongly decreased in intestinal of chronically SIVmac-infected macaques. Systemic IgA titers correlated negatively with sCD14 levels in SIVmac infection. Our data suggest an indirect impact of NK cell-mediated viral control in mesLN during SIVagm infection on preserved BCF function and IgA production in intestinal tissues.
Published: 2021

9. SARS-CoV-2 viral dynamics in non-human primates

Author: Andrés Pizzorno, Julien Lemaitre, Nathalie Dereuddre-Bosquet, Flora Donati, Raphael Ho Tsong Fang, Xavier de Lamballerie, Pauline Maisonnasse, Nidhal Kahlaoui, Olivier Terrier, Romain Marlin, Vanessa Contreras, Thibaut Naninck, Caroline Solas, Mélanie Albert, Bruno Hoen, Franck Touret, Antonio Gonçalves, Bruno Lina, Roger Le Grand, Catherine Chapon, Vincent Enouf, Angela Brisebarre, Sylvie van der Werf, Jeremie Guedj, Manuel Rosa Calatrava, Sylvie Behillil, 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, 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, Centre National de Référence des virus des infections respiratoires (dont la grippe) - National Reference Center Virus Influenzae [Paris] (CNR), Institut Pasteur [Paris], 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), 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), Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Virpath-Grippe, de l'émergence au contrôle -- Virpath-Influenza, from emergence to control (Virpath), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Plateforme de Microbiologie Mutualisée (PIBnet) - Mutualized Platform for Microbiology (P2M), 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), Centre National de Référence des Virus des Infections Respiratoires (dont la Grippe) [Lyon] (CNR), Institut des Agents Infectieux [Lyon] (IAI), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), This work was funded by the French national research agency (ANR) through the TheraCoV ANR-20-COVI-0018 (JG) and also by the Bill & Melinda Gates Foundation through INV-017335 (JG)., ANR-20-COVI-0018,TheraCoV,Dynamique virale au niveau individuel et populationnel : implications pour l'optimisation des stratégies antivirales(2020), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, 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), 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), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), 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), Centre National de Référence des Virus des Infections Respiratoires (dont la Grippe) [Lyon] (CNR - laboratoire associé), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Donati, Flora, and Dynamique virale au niveau individuel et populationnel : implications pour l'optimisation des stratégies antivirales - - TheraCoV2020 - ANR-20-COVI-0018 - COVID-19 - VALID
Subjects: Pulmonology, medicine.medical_treatment, Monkeys, Medical Conditions, 0302 clinical medicine, Nasopharynx, Public and Occupational Health, MESH: Animals, Biology (General), Mammals, Innate Immune System, MESH: Cytokines, Eukaryota, 3. Good health, [SDV] Life Sciences [q-bio], Trachea, Computational Theory and Mathematics, Modeling and Simulation, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Viral growth, Cytokines, SARS CoV 2, Viral load, Macaque, Primates, QH301-705.5, Immunology, Microbiology, Antiviral Agents, Respiratory Disorders, 03 medical and health sciences, Genetics, MESH: SARS-CoV-2, Molecular Biology, Ecology, Evolution, Behavior and Systematics, Experimental model, Organisms, Biology and Life Sciences, Molecular Development, Virology, MESH: Nasopharynx, Macaca fascicularis, 030104 developmental biology, Viral dynamics, MESH: Macaca fascicularis, Preventive Medicine, MESH: Disease Models, Animal, Digestive System, Basic reproduction number, Developmental Biology, RNA viruses, 0301 basic medicine, Coronaviruses, Physiology, viruses, [SDV]Life Sciences [q-bio], Respiratory System, Basic Reproduction Number, Virus Replication, Immune Physiology, Medicine and Health Sciences, MESH: COVID-19, 030212 general & internal medicine, Pathology and laboratory medicine, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Ecology, Viral Load, Medical microbiology, Vaccination and Immunization, Infectious Diseases, Cytokine, Vertebrates, Viruses, Anatomy, Pathogens, MESH: Viral Load, Research Article, MESH: Antiviral Agents, SARS coronavirus, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Biology, Virus, Cellular and Molecular Neuroscience, Antiviral Therapy, Old World monkeys, medicine, Animals, SARS-CoV-2, MESH: Virus Replication, Viral pathogens, COVID-19, Microbial pathogens, Disease Models, Animal, MESH: Basic Reproduction Number, Immune System, Amniotes, Respiratory Infections, Pharynx, Zoology, Viral Transmission and Infection, MESH: Trachea
Abstract: Non-human primates infected with SARS-CoV-2 exhibit mild clinical signs. Here we used a mathematical model to characterize in detail the viral dynamics in 31 cynomolgus macaques for which nasopharyngeal and tracheal viral load were frequently assessed. We identified that infected cells had a large burst size (>104 virus) and a within-host reproductive basic number of approximately 6 and 4 in nasopharyngeal and tracheal compartment, respectively. After peak viral load, infected cells were rapidly lost with a half-life of 9 hours, with no significant association between cytokine elevation and clearance, leading to a median time to viral clearance of 10 days, consistent with observations in mild human infections. Given these parameter estimates, we predict that a prophylactic treatment blocking 90% of viral production or viral infection could prevent viral growth. In conclusion, our results provide estimates of SARS-CoV-2 viral kinetic parameters in an experimental model of mild infection and they provide means to assess the efficacy of future antiviral treatments., Author summary Non-human primates infected with SARS-CoV-2 develop a mild infection resembling asymptomatic human infection. Here we used viral dynamic modelling to characterize the nasopharyngeal and tracheal viral loads. We found that viral load rapidly declined after peak viral load despite the absence of association between model parameters and immune markers. The within-host reproductive basic reproduction number was approximately equal to 6 and 4 in nasopharynx and trachea suggesting that a prophylactic therapy blocking viral entry or production with 90% efficacy could be sufficient to prevent viral growth and peak viral load.
Published: 2021

10. Two-component spike nanoparticle vaccine protects macaques from SARS-CoV-2 infection

Author: Anna Z Mykytyn, Max Crispin, Mathieu Claireaux, Karlijn van der Straten, Tom G. Caniels, Rashmi Ravichandran, Raphael Ho Tsong Fang, Kwinten Sliepen, Nisreen M.A. Okba, Mitch Brinkkemper, Nidhal Kahlaoui, Marlon de Gast, Rogier W. Sanders, Ilja Bontjer, Hannah L. Turner, Romain Marlin, Jelle van Schooten, Sylvie van der Werf, Meliawati Poniman, Godelieve J. de Bree, Yoann Aldon, Julien Lemaitre, Thibaut Naninck, Yasunori Watanabe, Roger Le Grand, Eric Ginoux, Ségolène Diry, Pauline Maisonnasse, Julien Villaudy, Edith E. Schermer, Julia M. Giezen, Vanessa Contreras, Bart L. Haagmans, Catherine Chapon, Gius Kerster, Philip J. M. Brouwer, Cynthia A. van der Linden, Yme U. van der Velden, Judith A. Burger, Andrew B. Ward, Virginie Chesnais, Mariëlle J. van Breemen, Marit J. van Gils, Marloes Grobben, Nathalie Dereuddre-Bosquet, Neil P. King, Joel D. Allen, Department of Medical Microbiology and Infection Prevention [Amsterdam], University of Amsterdam [Amsterdam] (UvA), 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, Life and Soft, University of Southampton, University of Oxford, The Scripps Research Institute [La Jolla, San Diego], Imperial College London, Amsterdam UMC - Amsterdam University Medical Center, Erasmus University Medical Center [Rotterdam] (Erasmus MC), University of Washington [Seattle], AIMM Therapeutics [Amsterdam, the Netherlands], 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), 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), This work was supported by a Netherlands Organisation for Scientific Research (NWO) Vici grant (to R.W.S.), the Bill & Melinda Gates Foundation through the Collaboration for AIDS Vaccine Discovery (CAVD) grants OPP1111923, OPP1132237, and INV-002022 (to R.W.S. and/or N.P.K.), INV-008352/OPP1153692 and OPP1196345/INV-008813 (to M.C.), and OPP1170236 (to A.B.W.), the Fondation Dormeur, Vaduz (R.W.S. and to M.J.v.G.) and Health-Holland PPS-allowance LSHM20040 (to M.J.v.G.), the University of Southampton Coronavirus Response Fund (M.C.), and the Netherlands Organisation for Health Research and Development ZONMW (B.L.H). M.J.v.G. is a recipient of an AMC Fellowship from Amsterdam UMC and a COVID-19 grant from the Amsterdam Institute for Infection and Immunity. R.W.S. and M.J.v.G. are recipients of support from the University of Amsterdam Proof of Concept fund (contract 200421) as managed by Innovation Exchange Amsterdam (IXA). The Infectious Disease Models and Innovative Therapies (IDMIT) research infrastructure is supported by the Programme Investissements d’Avenir, managed by the National Research Agency (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 non-human primate study received financial support from REACTing, the ANR (AM-CoV-Path), and the European Infrastructure TRANSVAC2 (730964)., ANR-11-INBS-0008,IDMIT,Infrastructure nationale pour la modélisation des maladies infectieuses humaines(2011), ANR-20-COVI-0021,AM-Cov-Path,Pathogénèse de l'infection SARS-Cov-2 dans un modèle de primates non humains : un modèle pour les traitements et la prévention(2020), European Project: 730964, H2020, RIA,H2020-INFRAIA-2016-1,TRANSVAC2(2017), Graduate School, AII - Infectious diseases, Medical Microbiology and Infection Prevention, Experimental Immunology, Infectious diseases, APH - Aging & Later Life, APH - Global Health, and Virology
Subjects: T-Lymphocytes, viruses, [SDV]Life Sciences [q-bio], Disease, Public administration, Mice, 0302 clinical medicine, vaccine, Pandemic, antibodies, Spike (database), Neutralizing antibody, 0303 health sciences, B-Lymphocytes, Mice, Inbred BALB C, biology, Transmission (medicine), Viral Load, protection, Models, Animal, Spike Glycoprotein, Coronavirus, Christian ministry, Rabbits, Antibody, Viral load, Healthcare system, COVID-19 Vaccines, Coronavirus disease 2019 (COVID-19), macaques, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Article, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Acquired immunodeficiency syndrome (AIDS), Immunity, Political science, medicine, Animals, 030304 developmental biology, B cells, SARS-CoV-2, Conflict of interest, Spike Protein, COVID-19, medicine.disease, Antibodies, Neutralizing, Virology, immunity, Macaca fascicularis, Immunization, Infectious disease (medical specialty), biology.protein, nanoparticles, 030217 neurology & neurosurgery
Abstract: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is continuing to disrupt personal lives, global healthcare systems, and economies. Hence, there is an urgent need for a vaccine that prevents viral infection, transmission, and disease. Here, we present a two-component protein-based nanoparticle vaccine that displays multiple copies of the SARS-CoV-2 spike protein. Immunization studies show that this vaccine induces potent neutralizing antibody responses in mice, rabbits, and cynomolgus macaques. The vaccine-induced immunity protects macaques against a high-dose challenge, resulting in strongly reduced viral infection and replication in the upper and lower airways. These nanoparticles are a promising vaccine candidate to curtail the SARS-CoV-2 pandemic., Graphical Abstract, Brouwer et al. present preclinical evidence in support of a COVID-19 vaccine candidate, designed as a self-assembling two-component protein nanoparticle displaying multiple copies of the SARS-CoV-2 spike protein, which induces strong neutralizing antibody responses and protects from high-dose SARS-CoV-2 challenge.
Published: 2021

11. Intranasal inoculation with Bordetella pertussis confers protection without inducing classical whooping cough in baboons

Author: Thibaut Naninck, Loïc Coutte, Aurélie Hébert-Ribon, Vanessa Contreras, Roger Le Grand, Sébastien Langlois, Magali Pelletier, Camille Locht, Nathalie Reveneau, and Catherine Chapon
Subjects: Microbiology (medical), Bordetella pertussis, QH426-470, Microbiology, Pathogenesis, 03 medical and health sciences, Immunology and Microbiology (miscellaneous), Pertussis, Baboons, Immunity, In vivo, Genetics, Medicine, Seroconversion, Whooping cough, 030304 developmental biology, Non-human primates, 0303 health sciences, biology, 030306 microbiology, business.industry, Respiratory infection, respiratory system, biology.organism_classification, medicine.disease, QR1-502, 3. Good health, Infectious Diseases, Immunology, Nasal administration, business
Abstract: Background The resurgence of whooping cough in many countries highlights the crucial need for a better understanding of the pathogenesis of respiratory infection by Bordetella pertussis. Exposure of baboons to B. pertussis by the intranasal and intra-tracheal routes is a recently described preclinical model that reproduces both B. pertussis infection of humans and whooping cough disease. Here, we tested both intranasal and intranasal+intra-tracheal exposure routes and assessed their impact on disease development and immunity. Methods Young baboons were intranasally exposed to the B1917 clinical isolate, representative of circulating strains in Europe, or its green-fluorescent protein expressing derivative. Animals were followed for pertussis symptoms and bacterial colonization and by in vivo probe-based confocal laser endomicroscopy (pCLE) imaging. Sero-conversion and protection against subsequent infection were then evaluated. Results Seroconversion and bacterial colonization of both the nasopharynx and trachea was observed in baboons exposed to B. pertussis by the intranasal route only, and also in those animals challenged by both the intranasal and intra-tracheal routes together. However, baboons exposed solely by the intranasal route developed only mild clinical symptoms, with no paroxysmal cough. These animals were protected against re-infection by B. pertussis. Conclusions Intranasal exposure of baboons to B. pertussis does not induce disease but elicits immune mechanisms that protect them from subsequent exposure to the bacteria. These findings suggest that the intranasal route of inoculation in this non-human primate model could be used in the pre-clinical evaluation of nasal candidate vaccines against pertussis.
Published: 2021
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12. Non-human Primate Determinants of Natural Killer Cells in Tissues at Steady-State and During Simian Immunodeficiency Virus Infection

Author: Anne Sophie Beignon, Vanessa Contreras, Michaela Müller-Trutwin, Roger Le Grand, Beatrice Jacquelin, Philippe Rascle, Jean-Louis Palgen, Nicolas Huot, Caroline Petitdemange, Christiane Stahl-Hennig, HIV, Inflammation et persistance, Institut Pasteur [Paris], Université Paris Diderot, Sorbonne Paris Cité, Paris, France, Université Paris Diderot - Paris 7 (UPD7), 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, Deutsches Primatenzentrum, Leibniz-Institut Primatenforschung (DPZ), NH was supported by the VRI Labex, the Fondation Beytout, and Institut Pasteur. PR was a recipient of a Ph.D. fellowship from the University Paris Diderot, Sorbonne Paris Cité, and also supported by the National Institutes of Health (R01AI143457). We would like to acknowledge grant support from French National Agency for Research on AIDS, the National Institutes of Health (R01AI143457), the Vaccine Research Institute, the Fondation J. Beytout, and the Fondation Les Ailes to MM-T. We gratefully acknowledge the support to IDMIT from the French government: Investments for the Future program for infrastructures (PIA) through the ANR-11-INBS-0008 grant as well as from the PIA grant ANR-10-EQPX-02-01 to the FlowCyTech facility at IDMIT., We are grateful for the excellent help from the veterinarians and staff at the IDMIT Center (Benoit Delache, Jean-Marie Helies, Raphaël Ho Tsong Fang, and Julie Morin). We thank M. Mietsch and M. Daskalaki for comprehensive veterinary support and S. Heine, J. Hampe, and N. Leuchte for excellent technical assistance., ANR-11-INBS-0008,IDMIT,Infrastructure nationale pour la modélisation des maladies infectieuses humaines(2011), ANR-10-EQPX-0002,FlowCyTech,Plateforme de phénotypage en Mass cytométrie pour l'analyse multiparamétrique de biomarqueurs complexes de l'efficacité de nouvelles stratégies thérapeutiques ou vaccinales(2010), HIV, Inflammation et persistance - HIV, Inflammation and Persistence, and Institut Pasteur [Paris] (IP)
Subjects: 0301 basic medicine, Primates, Receptors, CXCR5, lcsh:Immunologic diseases. Allergy, Lymphoid Tissue, [SDV]Life Sciences [q-bio], Immunology, HIV Infections, NK cells, medicine.disease_cause, CXCR3, Immunophenotyping, 03 medical and health sciences, 0302 clinical medicine, Intestinal mucosa, Species Specificity, Immunity, biology.animal, medicine, Immunology and Allergy, Animals, Humans, tissue resident, Cells, Cultured, Acquired Immunodeficiency Syndrome, biology, Natural Cytotoxicity Triggering Receptor 2, HIV, Simian immunodeficiency virus, lymph node, biology.organism_classification, Virology, 3. Good health, CXCR5, Killer Cells, Natural, Rhesus macaque, 030104 developmental biology, SIV, Organ Specificity, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, HIV-1, NKp44, gut, Simian Immunodeficiency Virus, African Green Monkey, lcsh:RC581-607, CD8, 030215 immunology, Baboon
Abstract: International audience; Natural killer (NK) cells play essential roles in immunity to viruses and tumors. Their function is genetically determined but also modulated by environmental factors. The distribution and functional regulation of these cells vary depending on the tissue. NK cell behavior in lymphoid tissues is so far understudied. Non-human primate (NHP) models are essential for the development of therapies and vaccines against human diseases, and access to NHP tissues allows insights into spatial regulations of NK cells. Here, we investigated tissue-specific parameters of NK cells from NHP species, i.e., cynomolgus macaque (Macaca fascicularis), African green monkey (Chlorocebus sabaeus), rhesus macaque (Macaca mulatta), and baboon (Papio anubis). By comprehensive multidimensional analysis of NK cells from secondary lymphoid organs, intestinal mucosa, liver, and blood, we identified tissue-and species-specific patterns of NK cell frequencies, phenotypes, and potential activity. Also, we defined the tissue-specific characteristics of NK cells during infection by the simian immunodeficiency virus. Altogether, our results provide a comprehensive anatomic analysis of NK cells in different tissues of primates at steady-state and during a viral infection.
Published: 2020

13. Viral dynamic modeling of SARS-CoV-2 in non-human primates

Author: Antonio Gonçalves, Pauline Maisonnasse, Flora Donati, Mélanie Albert, Sylvie Behillil, Vanessa Contreras, Thibaut Naninck, Romain Marlin, Caroline Solas, Andres Pizzorno, Julien Lemaitre, Nidhal Kahlaoui, Olivier Terrier, Raphael Ho Tsong Fang, Vincent Enouf, Nathalie Dereuddre-Bosquet, Angela Brisbarre, Franck Touret, Catherine Chapon, Bruno Hoen, Bruno Lina, Manuel Rosa-Calatrava, Xavier de Lamballerie, France Mentré, Roger Le Grand, Sylvie van der Werf, and Jeremie Guedj
Subjects: business.industry, viruses, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Medicine, business, Virology
Abstract: Non-human primates infected with SARS-CoV-2 exhibit mild clinical signs. Here we used a mathematical model to characterize in detail the viral dynamics in 31 cynomolgus macaques infected with 106 pfu of SARS-CoV-2 for which nasopharyngeal and tracheal viral load were frequently assessed. We identified that infected cells had a large daily viral production (>104 virus) and a within-host reproductive basic number of 6 and 4 in nasopharyngeal and tracheal compartment, respectively. After peak viral load, infected cells were rapidly cleared with a half-life of 9 hours, with no significant association between cytokine elevation and clearance. Translating our model to the context of human-to-human infection, human mild infection may be characterized by a peak occurring 4 days after infection, a viral shedding of ~11 days and a generation time of 4 days. These results improve the understanding of SARS-CoV-2 viral replication and better understand the infection to SARS-CoV-2 in humans.
Published: 2020

14. Hydroxychloroquine in the treatment and prophylaxis of SARS-CoV-2 infection in non- human primates

Author: Angela Brisebarre, Jeremie Guedj, Manuel Rosa Calatrava, Bruno Lina, Julien Lemaitre, Romain Marlin, Raphael Ho Tsong Fan, Vanessa Contreras, Catherine Chapon, Roger Le Grand, Antonio Gonçalves, Caroline Solas, Thibaut Naninck, Nathalie Bosquet, Bruno Hoen, Sylvie van der Werf, Sylvie Behillil, Nidhal Kahlaoui, Olivier Terrier, Vincent Enouf, Pauline Maisonnasse, Andrés Pizzorno, Xavier de Lamballerie, and Franck Toure
Subjects: business.industry, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Medicine, Hydroxychloroquine, business, Virology, medicine.drug
Abstract: COVID-19 has become a pandemic that has caused over 200,000 deaths worldwide, with no antiviral drug or vaccine yet available. Several clinical studies are ongoing to evaluate the efficacy of repurposed drugs that have demonstrated antiviral efficacy in vitro. Among these candidates, hydroxychloroquine (HCQ) has been given to thousands of individuals worldwide but definitive evidence for HCQ efficacy in treatment of COVID-19 is still missing.We evaluated the antiviral activity of HCQ both in vitro and in SARS-CoV-2-infected macaques. HCQ showed antiviral activity in monkey African green monkey kidney (VeroE6) cells but not in a model of reconstituted human airway epithelium. In macaques, we tested different treatment strategies in comparison to placebo, before and after peak viral load, alone or in combination with azithromycin (AZTH). Neither HCQ nor HCQ+AZTH showed a significant effect on the viral load levels in any of the tested compartments. When the drug was used as a pre-exposure prophylaxis (PrEP), HCQ did not confer protection against acquisition of infection.Our findings do not support the use of HCQ, either alone or in combination with AZTH, as an antiviral treatment for COVID-19 in humans.
Published: 2020

15. Innate and secondary humoral responses are improved by increasing the time between MVA vaccine immunizations

Author: Yves Levy, Roger Le Grand, Nathalie Dereuddre-Bosquet, Antonio Cosma, Vanessa Contreras, Nicolas Tchitchek, Anne-Sophie Beignon, André Rodriguez-Pozo, Hadjer Abdelhouahab, Frédéric Martinon, Quentin Jouhault, Jean-Louis Palgen, Université Paris-Sud - Paris 11 - Faculté de médecine (UP11 UFR Médecine), Université Paris-Sud - Paris 11 (UP11), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), U1184 IMVA-HB/IDMIT, Infectious Diseases Models for Innovative Therapies (IDMIT), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Immunologie des Maladies Virales et Autoimmunes (IMVA - U1184), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Henri Mondor [Créteil], 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, Immunologie - Immunopathologie - Immunothérapie [CHU Pitié Salpêtrière] (I3), CHU Charles Foix [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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), 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, and Tchitchek, Nicolas
Subjects: lcsh:Immunologic diseases. Allergy, 0301 basic medicine, Modified vaccinia Ankara, Myeloid, [SDV.IMM] Life Sciences [q-bio]/Immunology, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Immunology, lcsh:RC254-282, Article, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Immunity, medicine, Pharmacology (medical), Innate immunity, Pharmacology, Vaccines, Innate immune system, business.industry, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, 3. Good health, 030104 developmental biology, Infectious Diseases, medicine.anatomical_structure, Cytokine, chemistry, Immunization, Humoral immunity, [SDV.IMM]Life Sciences [q-bio]/Immunology, Vaccinia, lcsh:RC581-607, business, 030215 immunology
Abstract: Comprehending the mechanisms behind the impact of vaccine regimens on immunity is critical for improving vaccines. Indeed, the time-interval between immunizations may influence B and T cells, as well as innate responses. We compared two vaccine schedules using cynomolgus macaques immunized with an attenuated vaccinia virus. Two subcutaneous injections 2 weeks apart led to an impaired secondary antibody response and similar innate myeloid responses to both immunizations. In contrast, a delayed boost (2 months) improved the quality of the antibody response and involved more activated/mature innate cells, induced late after the prime and responding to the recall. The magnitude and quality of the secondary antibody response correlated with the abundance of these neutrophils, monocytes, and dendritic cells that were modified phenotypically and enriched prior to revaccination at 2 months, but not 2 weeks. These late phenotypic modifications were associated with an enhanced ex vivo cytokine production (including IL-12/23 and IL-1β) by PBMCs short after the second immunization, linking phenotype and functions. This integrated analysis reveals a deep impact of the timing between immunizations, and highlights the importance of early but also late innate responses involving phenotypical changes, in shaping humoral immunity.
Published: 2020

16. Anti-MOG autoantibodies pathogenicity in children and macaques demyelinating diseases

Author: Joanna Demilly, Julie Massonneau, Romain Marignier, Roger LeGrand, Jean Boutonnat, Philippe Hantraye, Bert A. 't Hart, Nicolas Tchitchek, Audrey Perrin, Julien Flament, Ché Serguera, Vanessa Contreras, Carole Leroy, Lev Stimmer, Claire-Maëlle Fovet, Pascale Chrétien, Philippe Horellou, Kumaran Deiva, Clovis Adam, Service MIRCEN (MIRCEN), Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie François JACOB (JACOB), 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)-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 du Cerveau = Paris Brain Institute (ICM), 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], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut de Biologie François JACOB (JACOB), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Infectious Diseases Models for Innovative Therapies (IDMIT), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Immunologie des Maladies Virales et Autoimmunes (IMVA - U1184), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Immunologie - Immunopathologie - Immunothérapie [CHU Pitié Salpêtrière] (I3), CHU Charles Foix [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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Hospices Civils de Lyon (HCL), Groupe Hospitalier Universitaire Paris-Sud (GHUPS), Biomedical Primate Research Centre [Rijswijk] (BPRC), University Medical Center Groningen [Groningen] (UMCG), Translational Innovation in Medicine and Complexity / Recherche Translationnelle et Innovation en Médecine et Complexité - UMR 5525 (TIMC ), 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)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA), CHU Grenoble, Hôpital Bicêtre, INSERM, CEA, ANRS (France Recherche Nord&Sud Sida-HIV Hépatites), Molecular Neuroscience and Ageing Research (MOLAR), Modélisation des biothérapies, Molecular Imaging Research Center, Fontenay aux Roses, Université Paris-Saclay-Institut de Biologie François JACOB (JACOB), Immunologie antivirale systémique et cérébrale, Université Paris-Sud - Paris 11 (UP11)-IFR93-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de recherche Virologie et Immunologie Moléculaires (VIM), Institut National de la Recherche Agronomique (INRA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut d'Imagerie BioMédicale (I2BM), Pierre Wertheimer, Département de Neurologie, Thérapeutique Recombinante Expérimentale (TIMC-IMAG-TheREx), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Service d'Anatomie Pathologique, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Bicêtre, Flament, Julien, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Unité de recherche Virologie et Immunologie Moléculaires (VIM (UR 0892)), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-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)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-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)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre
Subjects: Male, Neurology, Brain inflammation, [SDV]Life Sciences [q-bio], lcsh:RC346-429, 0302 clinical medicine, immune system diseases, Child, 0303 health sciences, biology, EAE, General Neuroscience, Experimental autoimmune encephalomyelitis, MULTIPLE-SCLEROSIS, Pathophysiology, 3. Good health, [SDV] Life Sciences [q-bio], EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS, Child, Preschool, Cytokines, Female, Antibody, Demyelination, medicine.medical_specialty, Encephalomyelitis, Autoimmune, Experimental, Adolescent, Immunology, MODELS, Complement, CSF, Myelin oligodendrocyte glycoprotein, 03 medical and health sciences, Cellular and Molecular Neuroscience, MYELIN OLIGODENDROCYTE GLYCOPROTEIN, medicine, Animals, Humans, lcsh:Neurology. Diseases of the nervous system, 030304 developmental biology, Autoantibodies, business.industry, Multiple sclerosis, Research, Autoantibody, Anti-MOG IgG, medicine.disease, Pathogenicity, nervous system diseases, nervous system, ANTIBODIES, biology.protein, Macaca, Myelin-Oligodendrocyte Glycoprotein, business, 030217 neurology & neurosurgery, Demyelinating Diseases
Abstract: Background Autoantibodies against myelin oligodendrocyte glycoprotein (anti-MOG-Abs) occur in a majority of children with acquired demyelinating syndromes (ADS) and physiopathology is still under investigation. As cynomolgus macaques immunized with rhMOG, all develop an experimental autoimmune encephalomyelitis (EAE), we assessed relatedness between anti-MOG-Abs associated diseases in both species. Methods The study includes 27 children followed for ADS and nine macaques with rhMOG-induced EAE. MRI lesions, cytokines in blood, and CSF at onset of ADS or EAE, as well as histopathological features of brain lesions were compared. Results Twelve children with anti-MOG-Abs ADS (ADS MOG+) and nine macaques with EAE, presented increased IL-6 and G-CSF in the CSF, whereas no such signature was found in 15 ADS MOG−. Furthermore, IgG and C1q were associated to myelin and phagocytic cells in brains with EAE (n = 8) and in biopsies of ADS MOG+ (n = 2) but not ADS MOG− children (n = 1). Macaque brains also revealed prephagocytic lesions with IgG and C1q depositions but no leukocyte infiltration. Conclusions Children with ADS MOG+ and macaques with EAE induced with rhMOG, present a similar cytokine signature in the CSF and a comparable aspect of brain lesions indicating analogous pathophysiological processes. In EAE, prephagocytic lesions points at IgG as an initial effector of myelin attack. These results support the pertinence of modeling ADS MOG+ in non-human primates to apprehend the natural development of anti-MOG-associated disease, find markers of evolution, and above all explore the efficacy of targeted therapies to test primate-restricted molecules.
Published: 2019

17. Targeting MOG to skin macrophages prevents EAE in macaques through TGFβ-induced peripheral tolerance

Author: Bert A. 't Hart, Peter Klucar, Audrey Hubert, Carole Leroy, Sabine Tricot, Julie Massonneau, Gerard Zurawski, Claire Maelle Fovet, Sandra Zurawski, Philippe Horellou, Kumaran Deiva, Catherine Chapon, Nabila Sediki, Roger Le Grand, Julien Flament, Vanessa Contreras, Che Serguera, Sangkon Oh, Nicolas Tchitchek, and Lev Stimmer
Subjects: 0303 health sciences, Antigen Targeting, biology, business.industry, medicine.medical_treatment, Peripheral tolerance, FOXP3, hemic and immune systems, 3. Good health, Myelin oligodendrocyte glycoprotein, nervous system diseases, 03 medical and health sciences, 0302 clinical medicine, Cytokine, Antigen, nervous system, immune system diseases, Immunology, biology.protein, Medicine, IL-2 receptor, business, Antigen-presenting cell, 030304 developmental biology, 030215 immunology
Abstract: To study the effect of vaccination on tolerization to the myelin antigen MOG we used a macaque model of experimental autoimmune encephalitis (EAE) in which immunization with recombinant human myelin oligodendrocyte glycoprotein (rhMOG) elicits brain inflammation and demyelination mediated by MOG-specific autoreactive CD4+ T lymphocytes and anti-MOG IgG. For antigen targeting to tolerizing antigen presenting cells, we used a recombinant antibody directed to the Dendritic Cells (DC)-Asialoglycoprotein receptor (DC-ASGPR). The intradermal administration of an anti-DC-ASGPR-MOG fusion protein, but not a control anti-DC-ASGPR-PSA (prostate specific antigen) protein, protected monkeys committed to develop EAE. Although effective treatment did not modify anti-MOG IgG production, it prevented the CD4+ T lymphocyte activation and pro-inflammatory cytokine production. Moreover, animals treated with anti-DC-ASGPR-MOG experienced a rise of MOG-specific CD4+CD25+FOXP3+CD39+ regulatory T cells as well as a TGFβ1, TGFβ2 and IL-8 upsurge after rhMOG re-immunization. Our results indicate that the pathogenicity of autoantibodies directed to MOG is mitigated in the presence of MOG-specific regulatory lymphocytes. This vaccination scheme appears suitable to treat relapsing autoimmune diseases with identified autoantigens such as that harboring anti-MOG or anti-AQP4 autoantibodies.
Published: 2019
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18. Recombinant Haemagglutinin Derived From the Ciliated Protozoan Tetrahymena thermophila Is Protective Against Influenza Infection

Author: Karina Jawinski, Marcus Hartmann, Charanjit Singh, Ekaterina Kinnear, David C. Busse, Annalisa Ciabattini, Fabio Fiorino, Donata Medaglini, Claudia Maria Trombetta, Emanuele Montomoli, Vanessa Contreras, Roger Le Grand, Celine Coiffier, Charlotte Primard, Bernard Verrier, John S. Tregoning, and Commission of the European Communities
Subjects: 0301 basic medicine, lcsh:Immunologic diseases. Allergy, Antigenicity, Polyesters, medicine.medical_treatment, Immunology, vaccine manufacture, Nod2 Signaling Adaptor Protein, Hemagglutinin Glycoproteins, Influenza Virus, Context (language use), Biology, Antibodies, Viral, Madin Darby Canine Kidney Cells, Tetrahymena thermophila, law.invention, Mice, 03 medical and health sciences, protozoa, Dogs, 0302 clinical medicine, Immune system, Orthomyxoviridae Infections, Antigen, adjuvant, law, medicine, influena virus, nanoparticle, Animals, Immunology and Allergy, Original Research, Mice, Inbred BALB C, Viral Vaccine, Tetrahymena, virus diseases, biology.organism_classification, Virology, Recombinant Proteins, 3. Good health, 030104 developmental biology, 1107 Immunology, Influenza Vaccines, Recombinant DNA, Macaca, Female, lcsh:RC581-607, Adjuvant, 030215 immunology
Abstract: Current influenza vaccines manufactured using eggs have considerable limitations, both in terms of scale up production and the potential impact passaging through eggs can have on the antigenicity of the vaccine virus strains. Alternative methods of manufacture are required, particularly in the context of an emerging pandemic strain. Here we explore the production of recombinant influenza haemagglutinin using the ciliated protozoan Tetrahymena thermophila. For the first time we were able to produce haemagglutinin from both seasonal influenza A and B strains. This ciliate derived material was immunogenic, inducing an antibody response in both mice and non-human primates. Mice immunized with ciliate derived haemagglutinin were protected against challenge with homologous influenza A or B viruses. The antigen could also be combined with submicron particles containing a Nod2 ligand, significantly boosting the immune response and reducing the dose of antigen required. Thus, we show that Tetrahymena can be used as a manufacturing platform for viral vaccine antigens.
Published: 2019

19. Bluetongue Virus Targets Conventional Dendritic Cells in Skin Lymph

Author: Stéphan Zientara, Michel Bonneau, Peter P. C. Mertens, Haru-Hisa Takamatsu, Céline Urien, Behzad Hemati, Emmanuel Bréard, Vanessa Contreras, Corinne Sailleau, Isabelle Schwartz-Cornil, Unité de recherche Virologie et Immunologie Moléculaires (VIM (UR 0892)), Institut National de la Recherche Agronomique (INRA), UE 1298 Unité Commune d'Expérimentation Animale, Institute for Animal Health, Virologie, École nationale vétérinaire d'Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA)-Agence Française de Sécurité Sanitaire des Aliments (AFSSA), Islamic Azad University-Karaj Branch, EU Commission, BBSRC, Defra (United Kingdom), and Agence Nationale for Research (Genanimal program, France)
Subjects: CD4-Positive T-Lymphocytes, 040301 veterinary sciences, Immunology, CD8-Positive T-Lymphocytes, Biology, Microbiology, Virus, 0403 veterinary science, Interferon-gamma, Viral Proteins, 03 medical and health sciences, Immune system, Immunity, Interferon, Virology, medicine, Animals, Lymph node, Cell Proliferation, Skin, 030304 developmental biology, 0303 health sciences, Sheep, Orbivirus, Interleukins, Dendritic Cells, 04 agricultural and veterinary sciences, Dendritic cell, biology.organism_classification, 3. Good health, medicine.anatomical_structure, Insect Science, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, B7-1 Antigen, Pathogenesis and Immunity, RNA, Viral, Female, B7-2 Antigen, Lymph, Bluetongue virus, medicine.drug
Abstract: Bluetongue virus (BTV) is the etiological agent of bluetongue, a hemorrhagic disease of ruminants (particularly sheep), which causes important economic losses around the world. BTV is transmitted primarily via the bites of infected midges, which inject the virus into the ruminant's skin during blood feeding. The virus initially replicates in the draining lymph node and then disseminates to secondary organs where it induces edema, hemorrhages, and necrosis. In this study, we show that ovine conventional dendritic cells (cDCs) are the primary targets of BTV that contribute to the primary dissemination of BTV from the skin to draining lymph nodes. Lymph cDCs support BTV RNA and protein synthesis, as well as the production of infectious virus belonging to several different BTV serotypes, regardless of their level of attenuation. Afferent lymph cell subsets, other than cDCs, showed only marginal levels of BTV protein expression. BTV infection provoked a massive recruitment of cDCs to the sheep skin and afferent lymph, providing cellular targets for infection. Although BTV productively infects cDCs, no negative impact on their physiology was detected. Indeed, BTV infection and protein expression in cDCs enhanced their survival rate. Several serotypes of BTV stimulated the surface expression of the CD80 and CD86 costimulatory molecules on cDCs as well as the mRNA synthesis of cytokines involved in inflammation and immunity, i.e., interleukin-12 (IL-12), IL-1β, and IL-6. BTV-infected cDCs stimulated antigen-specific CD4 and CD8 proliferation as well as gamma interferon production. BTV initially targets cDCs while preserving their functional properties, reflecting the optimal adaptation of the virus to its host cells for its first spread.
Published: 2009

20. Delivering HIV Gagp24 to DCIR Induces Strong Antibody Responses $In\ Vivo$

Author: Anne-Laure Flamar, Jacques F. Banchereau, Frédéric Martinon, Sandra Zurawski, N Dereuddre-Bosquet, Gerard Zurawski, Yves Levy, Monica Montes, Vanessa Contreras, Roger Le Grand, Baylor Institute for Immunology Research (BIIR), Baylor College of Medecine, Vaccine Research Institute, Université Paris-Est, Faculté de Médecine, INSERM U955, and Assistance Publique-Hôpitaux de Paris, Groupe Henri-Mondor Albert-Chenevier, Service d'Immunologie Clinique, Créteil, France, Infectious Diseases Models for Innovative Therapies (IDMIT), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Immunologie des Maladies Virales et Autoimmunes (IMVA - U1184), Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut des Maladies Emergentes et des Thérapies Innovantes (IMETI), The research was supported by the Agence Nationale de Recherche pour le Sida et hepatites virales through the Vaccine Research Institute programme via a Collaborative Research Agreement (CRA 2007-291), and Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: CD4-Positive T-Lymphocytes, Male, medicine.drug_class, medicine.medical_treatment, Recombinant Fusion Proteins, [SDV]Life Sciences [q-bio], Antigen presentation, Antibody Affinity, HIV Core Protein p24, lcsh:Medicine, Epitopes, T-Lymphocyte, HIV Infections, T-Cell Antigen Receptor Specificity, Biology, HIV Antibodies, Monoclonal antibody, Epitope, Antigen, medicine, Animals, Humans, Avidity, Lectins, C-Type, Receptors, Immunologic, lcsh:Science, Immunization Schedule, Antigen Presentation, Multidisciplinary, Membrane Glycoproteins, Immunogenicity, lcsh:R, Virology, 3. Good health, Macaca fascicularis, Immunology, Antibody Formation, biology.protein, HIV-1, Leukocytes, Mononuclear, lcsh:Q, Immunization, Antibody, Immunoglobulin Heavy Chains, Adjuvant, Research Article
Abstract: International audience; Targeting dendritic cell-specific endocytic receptors using monoclonal antibodies fused to desired antigens is an approach widely used in vaccine development to enhance the poor immunogenicity of protein-based vaccines and to induce immune responses. Here, we engineered an anti-human DCIR recombinant antibody, which cross-reacts with the homologous cynomolgous macaque receptor and was fused via the heavy chain C-terminus to HIV Gagp24 protein (αDCIR.Gagp24). In vitro, αDCIR.Gagp24 expanded multifunctional antigen-specific memory CD4$^+$ T cells recognizing multiple Gagp24 peptides from HIV-infected patient peripheral blood mononuclear cells. In non human primates, priming with αDCIR.Gagp24 without adjuvant elicited a strong anti-Gagp24 antibody response after the second immunization, while in the non-targeted HIV Gagp24 protein control groups the titers were weak. The presence of the double-stranded RNA poly(I:C) adjuvant significantly enhanced the anti-Gagp24 antibody response in all the groups and reduced the discrimination between the different vaccine groups. The avidity of the anti-Gagp24 antibody responses was similar with either αDCIR.Gagp24 or Gagp24 immunization, but increased from medium to high avidity in both groups when poly(I:C) was co-administered. This data provides a comparative analysis of DC-targeted and non-targeted proteins for their capacity to induce antigen-specific antibody responses in vivo. This study supports the further development of DCIR-based DC-targeting vaccines for protective durable antibody induction, especially in the absence of adjuvant.
Published: 2015

21. HIV specific responses induced in nonhuman primates with ANRS HIV-Lipo-5 vaccine combined with rMVA-HIV prime or boost immunizations

Author: Roger Le Grand, Frédéric Martinon, Pascal Clayette, Rahima Yousfi, Yves Levy, Vanessa Contreras, Nathalie Dereuddre-Bosquet, Leslie Gosse, Marie-Laurence Baron, and Isabelle Mangeot
Subjects: Enzyme-Linked Immunospot Assay, HIV Antigens, T-Lymphocytes, Immunization, Secondary, Vaccinia virus, Biology, CD8-Positive T-Lymphocytes, HIV Antibodies, Virus, chemistry.chemical_compound, Interferon-gamma, Lipopeptides, Antigen, Acquired immunodeficiency syndrome (AIDS), medicine, Animals, AIDS Vaccines, Vaccines, Synthetic, General Veterinary, General Immunology and Microbiology, Immunogenicity, Public Health, Environmental and Occupational Health, Antibody titer, virus diseases, medicine.disease, Virology, Macaca fascicularis, Infectious Diseases, chemistry, Immunology, Molecular Medicine, Cytokines, Interleukin-2, Vaccinia
Abstract: We evaluated the immunogenicity of a prime/boost vaccine strategy combining 5 lipopeptides (HIV-Lipo-5) and a recombinant modified vaccinia virus Ankara (rMVA-HIV) in cynomolgus macaques. Both of these vaccine components deliver HIV LAI Gag, Pol, and Nef antigens. Systemic and local safety was excellent in all groups. Immunization with HIV-Lipo-5 alone induced significant serum anti-HIV antibody titers which were not modified by rMVA-HIV immunization. However, induction of T-cell responses, as measured by IFNγ and IL-2 producing cells upon short-term stimulation with HIV peptide pools, required combined immunization with rMVA-HIV. Responses were preferentially observed against Gag antigen. Interestingly, HIV-Lipo-5 efficiently primed HIV induced T-cell responses upon the injection of rMVA-HIV, which may help to reduce the required number of vector injections. Our results provide a rationale for the use of a strategy involving HIV-Lipo-5 priming followed by rMVA-HIV booster immunization as a prophylactic or therapeutic vaccine approach against HIV infection and AIDS.
Published: 2014

22. Expression of VP7, a Bluetongue virus group specific antigen by viral vectors: Analysis of the induced immune responses and evaluation of protective potential in sheep

Author: Anthony Relmy, Stéphan Zientara, Richard Thiéry, Cyril Viarouge, Eric Dubois, Jean-Michel Guibert, Bernard Klonjkowski, Gilles Meyer, Emmanuel Bréard, Gilles Foucras, Isabelle Schwartz-Cornil, Coraline Bouet-Cararo, Marion Szelechowski, Agathe Caruso, Sokunthea Top, Vanessa Contreras, Stéphane Bertagnoli, Corinne Bergeron, Jennifer Richardson, Alexandra Desprat, Virologie UMR1161 (VIRO), Institut National de la Recherche Agronomique (INRA)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-École nationale vétérinaire d'Alfort (ENVA), Unité de recherche Virologie et Immunologie Moléculaires (VIM (UR 0892)), Institut National de la Recherche Agronomique (INRA), Interactions hôtes-agents pathogènes [Toulouse] (IHAP), Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Centre de Physiopathologie Toulouse Purpan (CPTP), 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)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de pathologie des petits ruminants, Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), UE Network of Excellence, EPIZONE FOOD-CT-2006-016236, European Project: 245266,EC:FP7:KBBE,FP7-KBBE-2009-3,ORBIVAC(2010), École nationale vétérinaire - Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT), 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), ProdInra, Migration, and Development of Vaccines for bTV, EHDV and AHSV - ORBIVAC - - EC:FP7:KBBE2010-02-01 - 2014-01-31 - 245266 - VALID
Subjects: Male, Epidemiology, Applied Microbiology, T-Lymphocytes, Virologie, viruses, Gene Expression, Disease Vectors, Antibodies, Viral, 0403 veterinary science, fluids and secretions, ovin, Cricetinae, Medicine and Health Sciences, Vector (molecular biology), Immune Response, Antigens, Viral, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Immunity, Cellular, 0303 health sciences, Multidisciplinary, Orbivirus, biology, Viral Core Proteins, expression de transgène, virus diseases, Infectious Disease Immunology, 04 agricultural and veterinary sciences, Vaccination and Immunization, 3. Good health, Santé publique et épidémiologie, Veterinary Diseases, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Medicine, Female, Rabbits, Viral Vectors, Antibody, Research Article, Biotechnology, mouton, 040301 veterinary sciences, Science, Immunology, Genetic Vectors, Cross Reactions, Microbiology, Bluetongue, Vector Biology, Virus, Cell Line, Viral vector, orbivirus, 03 medical and health sciences, Dogs, Immune system, Antigen, Immunity, vaccin antiviral, Virology, Animals, 030304 developmental biology, Sheep, fièvre catarrhale ovine, Biology and Life Sciences, Viral Vaccines, Veterinary Virology, biology.organism_classification, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, biology.protein, Clinical Immunology, Veterinary Science, Immunization, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Viral Transmission and Infection, Bluetongue virus
Abstract: International audience; Bluetongue virus (BTV) is an economically important Orbivirus transmitted by biting midges to domestic and wild ruminants. The need for new vaccines has been highlighted by the occurrence of repeated outbreaks caused by different BTV serotypes since 1998. The major group-reactive antigen of BTV, VP7, is conserved in the 26 serotypes described so far, and its role in the induction of protective immunity has been proposed. Viral-based vectors as antigen delivery systems display considerable promise as veterinary vaccine candidates. In this paper we have evaluated the capacity of the BTV-2 serotype VP7 core protein expressed by either a non-replicative canine adenovirus type 2 (Cav-VP7 R-0) or a leporipoxvirus (SG33-VP7), to induce immune responses in sheep. Humoral responses were elicited against VP7 in almost all animals that received the recombinant vectors. Both Cav-VP7 R-0 and SG33-VP7 stimulated an antigen-specific CD4(+) response and Cav-VP7 R-0 stimulated substantial proliferation of antigen-specific CD8(+) lymphocytes. Encouraged by the results obtained with the Cav-VP7 R-0 vaccine vector, immunized animals were challenged with either the homologous BTV-2 or the heterologous BTV-8 serotype and viral burden in plasma was followed by real-time RT-PCR. The immune responses triggered by Cav-VP7 R-0 were insufficient to afford protective immunity against BTV infection, despite partial protection obtained against homologous challenge. This work underscores the need to further characterize the role of BTV proteins in cross-protective immunity.
Published: 2014

23. Canine recombinant adenovirus vector induces an immunogenicity-related gene expression profile in skin-migrated CD11b⁺ -type DCs

Author: Luc Jouneau, Stéphan Zientara, Vanessa Contreras, Isabelle Schwartz-Cornil, Coraline Bouet-Cararo, Mickael Bourge, Céline Urien, Bernard Klonjkowski, Michel Bonneau, Unité de recherche Virologie et Immunologie Moléculaires (VIM (UR 0892)), Institut National de la Recherche Agronomique (INRA), IMAGIF, Centre National de la Recherche Scientifique (CNRS), Université Paris Est, École nationale vétérinaire d'Alfort (ENVA), Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Virologie UMR1161 (VIRO), Institut National de la Recherche Agronomique (INRA)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-École nationale vétérinaire d'Alfort (ENVA), Agence Nationale pour la Recherche [ANR 06 GANI 015-03, ANR 09 BLAN 0073], and École nationale vétérinaire d'Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)
Subjects: SUBSETS, [SDV]Life Sciences [q-bio], Veterinary Microbiology, VACCINE, Gene Expression, Adenoviruses, Canine, Transcriptomes, 0302 clinical medicine, Cell Movement, Gene expression, Molecular Cell Biology, IMMUNE-RESPONSE, LYMPH DENDRITIC CELLS, RECEPTOR PATHWAY, SYSTEMS BIOLOGY, TYPE-35 VECTORS, IN-VITRO, EFFICACY, VIRUS, Immune Response, Skin, 0303 health sciences, Vaccines, Multidisciplinary, CD11b Antigen, Immunogenicity, Systems Biology, Vaccination, Genomics, Innate Immunity, 3. Good health, Medicine, Female, Integrin alpha Chains, Research Article, Science, Immune Cells, Genetic Vectors, Immunology, DNA, Recombinant, Antigen-Presenting Cells, chemical and pharmacologic phenomena, Biology, Microbiology, Viral vector, 03 medical and health sciences, Immune system, Dogs, Antigen, Immunity, Antigens, CD, Genome Analysis Tools, Virology, Animals, Humans, 030304 developmental biology, Sheep, Viral Vaccines, Dendritic Cells, Gene expression profiling, Clinical Immunology, Veterinary Science, Transcriptome, 030215 immunology
Abstract: International audience; Gene expression profiling of the blood cell response induced early after vaccination has previously been demonstrated to predict the immunogenicity of vaccines. In this study, we evaluated whether the analysis of the gene expression profile of skin-migrated dendritic cells (DCs) could be informative for the in vitro prediction of immunogenicity of vaccine, using canine adenovirus serotype 2 (CAV2) as vaccine vector. CAV2 has been shown to induce immunity to transgenes in several species including sheep and is an interesting alternative to human adenovirus-based vectors, based on the safety records of the parental strain in dogs and the lack of pre-existing immunity in non-host species. Skin-migrated DCs were collected from pseudo-afferent lymph in sheep. Both the CD11b(+)-type and CD103(+)-type skin-migrated DCs were transduced by CAV2. An analysis of the global gene response to CAV2 in the two skin DC subsets showed that the gene response in CD11b+-type DCs was far higher and broader than in the CD103(+)-type DCs. A newly released integrative analytic tool from Ingenuity systems revealed that the CAV2-modulated genes in the CD11b(+)-type DCs clustered in several activated immunogenicity-related functions, such as immune response, immune cell trafficking and inflammation. Thus gene profiling in skin-migrated DC in vitro indicates that the CD11b(+) DC type is more responsive to CAV2 than the CD103(+) DC type, and provides valuable information to help in evaluating and possibly improving viral vector vaccine effectiveness.
Published: 2012

24. Unraveling features of the natural MHC class II peptidome of skin-migrated dendritic cells

Author: Javier Collado, Michel Bonneau, Yannick Alexandre, Isabelle Schwartz-Cornil, Vanessa Contreras, Keith Ballingall, Laia Muixí, Dolores Jaraquemada, Universitat Autònoma de Barcelona (UAB), Unité de recherche Virologie et Immunologie Moléculaires (VIM (UR 0892)), Institut National de la Recherche Agronomique (INRA), Moredun Research Institute [Penicuik, UK] (MRI), Intervent Imaging Ctr, Partenaires INRAE, French National Institute of Agricultural Research, Spanish Ministry of Education [SAF2006-08928, AP2006-03101], and French Ministry of Superior Education and Research
Subjects: Proteomics, INDUCE TOLERANCE, T-Lymphocytes, [SDV]Life Sciences [q-bio], Autoantigens, Mass Spectrometry, ANTIGEN-PRESENTING CELLS, 0302 clinical medicine, DRAINING LYMPH-NODE, Cell Movement, Immunology and Allergy, Lymph node, Chromatography, High Pressure Liquid, AFFERENT LYMPH, IN-VIVO, 0303 health sciences, medicine.diagnostic_test, biology, Chemistry, EPITHELIAL-CELLS, General Medicine, Flow Cytometry, medicine.anatomical_structure, B-CELLS, Female, Lymph, skin, Genotype, Molecular Sequence Data, Immunology, Antigen presentation, Flow cytometry, 03 medical and health sciences, Antigen, MHC class I, medicine, Animals, Amino Acid Sequence, dendritic cells, REGULATORY T-CELLS, Antigen-presenting cell, 030304 developmental biology, MHC class II, peptide repertoire, Sheep, HLA-DR, Histocompatibility Antigens Class II, MASS-SPECTROMETRY, Leukocytes, Mononuclear, biology.protein, Lymph Nodes, Peptides, 030215 immunology
Abstract: International audience; Dendritic cells (DCs) migrating from peripheral tissues at steady state are considered the most efficient antigen-presenting cells (APCs) involved in the induction of peripheral T-cell tolerance via self-antigen presentation on MHC class II molecules. However, difficulties in obtaining sufficient numbers of such DCs have precluded previous analyses of their natural MHC class II peptidome in laboratory animals or humans. Here, we overcome this difficulty by collecting the large quantities of sheep DCs that migrate from the skin via the afferent lymphatics at steady state to the draining lymph node. We compared the repertoire of MHC class II-bound peptides from afferent lymph DCs with autologous APCs derived from peripheral blood. A large fraction of the MHC class II peptidome from skin DCs was derived from membrane-recycling proteins (59%) and from proteins of the antigen presentation machinery (50%), whereas these types of peptides constituted a more limited fraction in blood APCs (21 and 11%, respectively). One sheep cytokeratin peptide was identified in the skin DC peptidome indicating active processing of epithelium-derived antigens. Conversely, peptides derived from cytosolic and soluble antigens of the extracellular milieu were more represented in blood APCs than skin DCs. The biased peptidome of skin-migrated DCs indicates that these cells express a peptide repertoire for the generation of self-reactive and/or regulatory T cells mainly directed toward DC molecules from internal and external membranes and to a lesser extent toward antigens of the extracellular milieu, including some tissue-specific peptides.
Published: 2012

25. Targeting HIV Gag p24 to DICR on dendritic cells induces T cell and potent and long-lasting antibody responses in non-human primates

Author: Vanessa Contreras, I Mangeot, N Dereuddre-Bosquet, Jacques Banchereau, Gerald Zurawski, Yves Levy, Sangkon Oh, Anne-Laure Flamar, Frédéric Martinon, R Le Grand, S Zurawski, BMC, Ed., Baylor Institute for Immunology Research (BIIR), Baylor College of Medecine, Institut des Maladies Emergentes et des Thérapies Innovantes (IMETI), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-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), Service d'immunologie clinique [Créteil], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)
Subjects: medicine.medical_treatment, T cell, Peripheral blood mononuclear cell, law.invention, 03 medical and health sciences, law, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Virology, Medicine, Receptor, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, biology, 030306 microbiology, business.industry, ELISPOT, Fusion protein, 3. Good health, Cytokine, medicine.anatomical_structure, Infectious Diseases, Immunology, Poster Presentation, biology.protein, Recombinant DNA, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Antibody, business
Abstract: Methods We engineered an anti-human DCIR recombinant antibody cross-reacting with the cynomolgus macaque receptor fused via the heavy chain C-terminus to HIV-1 Gagp24 protein (anti-DCIR.Gagp24). HIV patient PBMC cultures were incubated with anti-DCIR and control hIgG4.Gagp24 fusion proteins. After 10 days, the total T cells were challenged with HIV Gagp24 peptide pools, and then antigen-specific cytokine production was detected using intracellular staining. Macaques were also immunized i.d. 3 times with anti-DCIR.Gagp24 or control hIgG4.Gagp24 with or without polyI:C. Gagp24-specific IgG titers from serum were measured by ELISA and the magnitude of the antigen-specific IFNg responses was assessed by ELISPOT.
Published: 2012

26. Canine adenoviruses elicit both humoral and cell-mediated immune responses against rabies following immunisation of sheep

Author: Noël Tordo, Corinne Jallet, Isabelle Schwartz-Cornil, Emmanuel Bréard, Stéphan Zientara, Bernard Klonjkowski, Jean Michel Guibert, Eric Dubois, Jennifer Richardson, Annie Fournier, Richard Thiéry, Vanessa Contreras, Coraline Bouet-Cararo, Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Unité de recherche Virologie et Immunologie Moléculaires (VIM), Institut National de la Recherche Agronomique (INRA), Stratégies Antivirales, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Unité de pathologie des petits ruminants, Unité de recherche Virologie et Immunologie Moléculaires (VIM (UR 0892)), and Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)
Subjects: CD4-Positive T-Lymphocytes, Male, Rabies, 040301 veterinary sciences, Genetic Vectors, Lymphocyte proliferation, Adenoviruses, Canine, CD8-Positive T-Lymphocytes, Antibodies, Viral, Vaccines, Attenuated, medicine.disease_cause, 0403 veterinary science, Interferon-gamma, 03 medical and health sciences, Immune system, medicine, Animals, Vector (molecular biology), Neutralizing antibody, Cell Proliferation, 030304 developmental biology, Duck embryo vaccine, Drug Carriers, Vaccines, Synthetic, 0303 health sciences, Sheep, General Veterinary, General Immunology and Microbiology, biology, Rabies virus, Public Health, Environmental and Occupational Health, 04 agricultural and veterinary sciences, Canine adenovirus, vaccine, ovine, medicine.disease, Antibodies, Neutralizing, Virology, 3. Good health, Vaccination, Infectious Diseases, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Rabies Vaccines, Vaccines, Inactivated, biology.protein, Molecular Medicine
Abstract: International audience; Safe and efficient vaccination is important for rabies prevention in domestic animals. Replicative vectors expressing the rabies virus glycoprotein, derived from canine adenovirus have been reported to be promising vaccines in various animal models. In this paper we compare the potential of a replicative and a non-replicative vector, both based on canine adenovirus type 2 and expressing the rabies glycoprotein. Upon inoculation in sheep, immune responses against the rabies virus protein elicited by recombinant vectors were monitored. All immunised sheep produced a rapid and potent neutralizing antibody response against rabies virus after a single inoculation of either replicative or non-replicative recombinant canine adenovirus type 2. In addition, the non-replicative vector expressing the rabies glycoprotein stimulated antigen-specific CD4(+) and CD8(+) lymphocyte proliferation as well as IFN-γ production. These results suggest that vectors derived from canine adenovirus 2 could be considered for the development of promising vaccines in the ruminant species.
Published: 2010

27. The XC chemokine receptor 1 is a conserved selective marker of mammalian cells homologous to mouse CD8alpha+ dendritic cells

Author: Marc Dalod, Anne Hosmalin, Karine Crozat, Thien-Phong Vu Manh, Jacqueline Marvel, Pierre Boudinot, Vincent Feuillet, Isabelle Schwartz-Cornil, Erwan Ventre, Rachel Guiton, Anne K. Storset, Vanessa Contreras, Thomas Baranek, Charles-Antoine Dutertre, Centre d'Immunologie de Marseille - Luminy (CIML), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Unité de recherche Virologie et Immunologie Moléculaires (VIM), Institut National de la Recherche Agronomique (INRA), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Immunité infection vaccination (I2V), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-IFR128-Institut National de la Santé et de la Recherche Médicale (INSERM), Norwegian School of Veterinary Science, Norvège, Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Unité de recherche Virologie et Immunologie Moléculaires (VIM (UR 0892)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Immunologie de Marseille - Luminy ( CIML ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Aix Marseille Université ( AMU ) -Centre National de la Recherche Scientifique ( CNRS ), Unité de recherche Virologie et Immunologie Moléculaires ( VIM ), Institut National de la Recherche Agronomique ( INRA ), Institut Cochin ( UM3 (UMR 8104 / U1016) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Immunité infection vaccination ( I2V ), Université Claude Bernard Lyon 1 ( UCBL ), and Université de Lyon-Université de Lyon-IFR128-Institut National de la Santé et de la Recherche Médicale ( INSERM )
Subjects: Chemokine, XCR1, T cell, Dipeptidyl Peptidase 4, Thrombomodulin, Immunology, chemical and pharmacologic phenomena, Biology, CD8-Positive T-Lymphocytes, Article, Receptors, G-Protein-Coupled, 03 medical and health sciences, Chemokine receptor, Mice, 0302 clinical medicine, Cross-Priming, Antigen, medicine, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, Immunology and Allergy, Animals, Humans, Listeriosis, RNA, Messenger, Receptor, Conserved Sequence, Phylogeny, 030304 developmental biology, Mammals, 0303 health sciences, Sheep, hemic and immune systems, Dendritic Cells, Virology, Cell biology, Chemokines, C, Killer Cells, Natural, medicine.anatomical_structure, Gene Expression Regulation, Antigens, Surface, biology.protein, [SDV.IMM]Life Sciences [q-bio]/Immunology, Immunologic Memory, CD8, Biomarkers, 030215 immunology, XCL1
Abstract: International audience; Human BDCA3+ dendritic cells (DCs) were suggested to be homologous to mouse CD8alpha+ DCs. We demonstrate that human BDCA3+ DCs are more efficient than their BDCA1+ counterparts or plasmacytoid DCs (pDCs) in cross-presenting antigen and activating CD8+ T cells, which is similar to mouse CD8alpha+ DCs as compared with CD11b+ DCs or pDCs, although with more moderate differences between human DC subsets. Yet, no specific marker was known to be shared between homologous DC subsets across species. We found that XC chemokine receptor 1 (XCR1) is specifically expressed and active in mouse CD8alpha+, human BDCA3+, and sheep CD26+ DCs and is conserved across species. The mRNA encoding the XCR1 ligand chemokine (C motif) ligand 1 (XCL1) is selectively expressed in natural killer (NK) and CD8+ T lymphocytes at steady-state and is enhanced upon activation. Moreover, the Xcl1 mRNA is selectively expressed at high levels in central memory compared with naive CD8+ T lymphocytes. Finally, XCR1-/- mice have decreased early CD8+ T cell responses to Listeria monocytogenes infection, which is associated with higher bacterial loads early in infection. Therefore, XCR1 constitutes the first conserved specific marker for cell subsets homologous to mouse CD8alpha+ DCs in higher vertebrates and promotes their ability to activate early CD8+ T cell defenses against an intracellular pathogenic bacteria.
Published: 2010

28. Bluetongue virus: virology, pathogenesis and immunity

Author: Philip S. Mellor, Florentina Pascale, Isabelle Schwartz-Cornil, Vanessa Contreras, Behzad Hemati, N. James MacLachlan, Emmanuel Bréard, Peter P. C. Mertens, and Stéphan Zientara
Subjects: Serotype, vaccin, viruses, ruminant, 0403 veterinary science, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], cytokine, bluetongue, 0303 health sciences, Orbivirus, biology, [SDV.BA]Life Sciences [q-bio]/Animal biology, 04 agricultural and veterinary sciences, Culicoides, 3. Good health, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, protéine, [SDV.IMM]Life Sciences [q-bio]/Immunology, Veterinary medicine and animal Health, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Antibody, 040301 veterinary sciences, Reoviridae, virus, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Arbovirus, Virus, Microbiology, orbivirus, 03 medical and health sciences, Immunity, medicine, Animals, 030304 developmental biology, Sheep, viral haemorrhagic disease, General Veterinary, Viral Vaccines, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, BLUETONGUE, ORBIVIRUS, ARBOVIRUS, VIRAL HAEMORRHAGIC DISEASE, RUMINANTS, medicine.disease, biology.organism_classification, Virology, [SDV.GEN.GA]Life Sciences [q-bio]/Genetics/Animal genetics, Médecine vétérinaire et santé animal, arbovirus, ruminants, biology.protein, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Bluetongue virus
Abstract: Bluetongue (BT) virus, an orbivirus of the Reoviridae family encompassing 24 known serotypes, is transmitted to ruminants via certain species of biting midges (Culicoides spp.) and causes thrombo-hemorrhagic fevers mainly in sheep. During the 20th century, BTV was endemic in sub-tropical regions but in the last ten years, new strains of BTV (serotypes 1, 2, 4, 8, 9, 16) have appeared in Europe leading to a devastating disease in naive sheep and bovine herds (serotype 8). BTV enters into insect cells via the viral inner core VP7 protein and in mammalian cells via the external capsid VP2 haemagglutinin, which is the major determinant of BTV serotype and neutralization. BTV replicates in mononuclear phagocytes and endothelial cells where it induces expression of inflammatory cytokines as well as apoptosis. BTV can remain as nonreplicating entities concealed in erythrocytes for up to five months. Homologous protection against one BTV serotype involves neutralizing antibodies and T cell responses directed to the external VP2 and VP5 proteins, whereas heterologous protection is supported by T cells directed to the NS1 non structural protein and inner core proteins. Classical inactivated vaccines directed to a specific serotype generate protective immunity and may help control current epidemic situations. New recombinant vaccine strategies that allow differentiating infected from vaccinated animals and that generate cross protective immunity are urgently needed to efficiently combat this worldwide threatening disease. bluetongue / orbivirus / arbovirus / viral haemorrhagic disease / ruminants
Published: 2008

29. Type I interferon producing cells (IPC) can gain lymph nodes via the afferent lymphatic route

Author: Jayne Hope, Stefan Chilmonczyk, A.-M. Balazuc, Claudia Bevilacqua, Vanessa Contreras, Alexandre Courbet, Béatrice Riteau, Artur Summerfield, Bernard Charley, Florentina Pascale, Isabelle Schwartz-Cornil, Mathieu Epardaud, and Michel Bonneau
Subjects: Pathology, medicine.medical_specialty, General Veterinary, Follicular dendritic cells, Immunology, Biology, CPG-oligonucleotide, Lymphatic system, Interferon, Afferent, medicine, Lymph node stromal cell, Lymph, medicine.drug
Published: 2009

30. Hydroxychloroquine use against SARS-CoV-2 infection in non-human primates

Author: Julien Lemaitre, Andrés Pizzorno, Thibaut Naninck, Nathalie Dereuddre-Bosquet, Bruno Hoen, Antonio Gonçalves, Roger Le Grand, Bruno Lina, Jeremie Guedj, Romain Marlin, Xavier de Lamballerie, Olivier Terrier, Catherine Chapon, Nidhal Kahlaoui, Vanessa Contreras, Manuel Rosa Calatrava, Franck Touret, Vincent Enouf, Angela Brisebarre, Sylvie Behillil, Caroline Solas, Sylvie van der Werf, Raphael Ho Tsong Fang, Pauline Maisonnasse, 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, 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, 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), 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), 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), Virpath-Grippe, de l'émergence au contrôle -- Virpath-Influenza, from emergence to control (Virpath), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Pasteur International Bioresources network (PIBNet), Plateforme de Microbiologie Mutualisée (PIBnet) - Mutualized Platform for Microbiology (P2M), 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), Hospices Civils de Lyon (HCL), Anthropologie bio-culturelle, Droit, Ethique et Santé (ADES), Aix Marseille Université (AMU)-EFS ALPES MEDITERRANEE-Centre National de la Recherche Scientifique (CNRS), This study received financial support from REACTing, the National Research Agency (ANR, AM-CoV-Path) and the European Union’s Horizon 2020 (H2020) research and innovation program Fight-nCov (101003555), European Union IMI2 program CARE (101005077) and the European Infrastructure TRANSVAC2 (730964). The virus stock was obtained through the EVAg platform (https://www.european-virus-archive.com/), funded by H2020 (653316). 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., ANR-21-CO14-0001,FCHG,GWAS francaise pour l'identification des facteurs génétiques de l'hôtes de la COVID19(2021), Université Paris-Saclay-Institut National de la Santé et de la Recherche Médicale (INSERM)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Université Sorbonne Paris Nord, 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) [Paris] (CNR), Institut Pasteur [Paris], Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Microbiologie mutualisée (Plate-forme) (P2M), Pasteur-Cnam risques infectieux et émergents (PACRI), Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut Pasteur [Paris], ANR-20-COVI-0021,AM-CoV-Path,Pathogenesis of SARS-Cov-2 infection in NHP model: insights for treatment and prevention, ANR-11-INBS-0008/11-INBS-0008,IDMIT,Infrastructure nationale pour la modélisation des maladies infectieuses humaines(2011), European Project: 101003555,H2020, RIA,H2020-SC1-PHE-CORONAVIRUS-2020,Fight-nCoV(2020), European Project: 101005077,H2020, IMI2-RIA,H2020-JTI-IMI2-2020-21-single-stage,CARE(2020), European Project: 730964, H2020, RIA,H2020-INFRAIA-2016-1,TRANSVAC2(2017), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Université Sorbonne Paris Nord, Centre National de Référence des virus des infections respiratoires (dont la grippe) - National Reference Center Virus Influenzae [Paris] (CNR), Aix Marseille Université (AMU)-Institut de Recherche pour le Développement (IRD)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM), Terrier, Olivier, Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, 0301 basic medicine, Time Factors, MESH: Treatment Failure, MESH: Coronavirus Infections, MESH: Hydroxychloroquine, Azithromycin, MESH: Chlorocebus aethiops, Chlorocebus aethiops, MESH: Respiratory Mucosa, MESH: Animals, Treatment Failure, media_common, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, MESH: Cytokines, Multidisciplinary, MESH: Kinetics, Viral Load, 3. Good health, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Cytokines, MESH: Betacoronavirus, Female, Coronavirus Infections, MESH: Viral Load, Viral load, Hydroxychloroquine, medicine.drug, Drug, MESH: Pandemics, medicine.drug_class, media_common.quotation_subject, Pneumonia, Viral, 030106 microbiology, MESH: Vero Cells, Respiratory Mucosa, In Vitro Techniques, Virus, Betacoronavirus, 03 medical and health sciences, MESH: Azithromycin, medicine, Animals, Humans, Pandemics, Vero Cells, MESH: In Vitro Techniques, MESH: Humans, SARS-CoV-2, business.industry, MESH: Time Factors, COVID-19, medicine.disease, MESH: Male, COVID-19 Drug Treatment, Disease Models, Animal, Kinetics, Macaca fascicularis, Pneumonia, 030104 developmental biology, MESH: Macaca fascicularis, MESH: Pneumonia, Viral, Immunology, Vero cell, Pre-Exposure Prophylaxis, Antiviral drug, MESH: Disease Models, Animal, business, MESH: Female, MESH: Pre-Exposure Prophylaxis
Abstract: International audience; Coronavirus disease 2019 (COVID-19) has rapidly become a global pandemic and no antiviral drug or vaccine is yet available for the treatment of this disease1-3. Several clinical studies are ongoing to evaluate the efficacy of repurposed drugs that have demonstrated antiviral efficacy in vitro. Among these candidates, hydroxychloroquine (HCQ) has been given to thousands of individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-the virus that causes COVID-19-worldwide but there is no definitive evidence that HCQ is effective for treating COVID-194-7. Here we evaluated the antiviral activity of HCQ both in vitro and in SARS-CoV-2-infected macaques. HCQ showed antiviral activity in African green monkey kidney cells (Vero E6) but not in a model of reconstituted human airway epithelium. In macaques, we tested different treatment strategies in comparison to a placebo treatment, before and after peak viral load, alone or in combination with azithromycin (AZTH). Neither HCQ nor the combination of HCQ and AZTH showed a significant effect on viral load in any of the analysed tissues. When the drug was used as a pre-exposure prophylaxis treatment, HCQ did not confer protection against infection with SARS-CoV-2. Our findings do not support the use of HCQ, either alone or in combination with AZTH, as an antiviral drug for the treatment of COVID-19 in humans.
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31. Non-human primate models of human respiratory infections

Author: Frédéric Ducancel, Pauline Maisonnasse, Laurent Vecellio, Vanessa Contreras, Marion Holzapfel, Roger Le Grand, Julien Lemaitre, Thibaut Naninck, Camille Bouillier, Frédéric Martinon, Philippe Huber, Nidhal Kahlaoui, Benoit Delache, Sabine Tricot, Justina Creppy, and Quentin Pascal
Subjects: 0301 basic medicine, medicine.medical_specialty, COVID-19 Vaccines, Coronavirus disease 2019 (COVID-19), Immunology, Respiratory tract, Article, 03 medical and health sciences, 0302 clinical medicine, Pandemic, Medicine, Animals, Humans, Potential source, Intensive care medicine, Molecular Biology, Infectious disease, Non human primate, Bacteria, Transmission (medicine), business.industry, SARS-CoV-2, COVID-19, Haplorhini, Non-human primate, Respiratory pathogens, Virus, Disease Models, Animal, 030104 developmental biology, Infectious disease (medical specialty), business, 030215 immunology, Infectious agent
Abstract: Respiratory pathogens represent a great burden for humanity and a potential source of new pandemics, as illustrated by the recent emergence of coronavirus disease 2019 (COVID-19). In recent decades, biotechnological advances have led to the development of numerous innovative therapeutic molecules and vaccine immunogens. However, we still lack effective treatments and vaccines against many respiratory pathogens. More than ever, there is a need for a fast, predictive, preclinical pipeline, to keep pace with emerging diseases. Animal models are key for the preclinical development of disease management strategies. The predictive value of these models depends on their ability to reproduce the features of the human disease, the mode of transmission of the infectious agent and the availability of technologies for monitoring infection. This review focuses on the use of non-human primates as relevant preclinical models for the development of prevention and treatment for human respiratory infections.
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31 results on '"Vanessa Contreras"'

1. Immunogenicity and efficacy of VLA2001 vaccine against SARS-CoV-2 infection in male cynomolgus macaques

2. Intradermal vaccination prevents anti-MOG autoimmune encephalomyelitis in macaquesResearch in context

3. Delivering HIV Gagp24 to DCIR Induces Strong Antibody Responses In Vivo.

4. Expression of VP7, a Bluetongue virus group specific antigen by viral vectors: analysis of the induced immune responses and evaluation of protective potential in sheep.

5. Canine recombinant adenovirus vector induces an immunogenicity-related gene expression profile in skin-migrated CD11b⁺ -type DCs.

6. Immunization with synthetic SARS-CoV-2 S glycoprotein virus-like particles protects macaques from infection

7. Targeting SARS-CoV-2 receptor-binding domain to cells expressing CD40 improves protection to infection in convalescent macaques

8. NK cell spatial dynamics and IgA responses in gut-associated lymphoid tissues during SIV infections

9. SARS-CoV-2 viral dynamics in non-human primates

10. Two-component spike nanoparticle vaccine protects macaques from SARS-CoV-2 infection

11. Intranasal inoculation with Bordetella pertussis confers protection without inducing classical whooping cough in baboons

12. Non-human Primate Determinants of Natural Killer Cells in Tissues at Steady-State and During Simian Immunodeficiency Virus Infection

13. Viral dynamic modeling of SARS-CoV-2 in non-human primates

14. Hydroxychloroquine in the treatment and prophylaxis of SARS-CoV-2 infection in non- human primates

15. Innate and secondary humoral responses are improved by increasing the time between MVA vaccine immunizations

16. Anti-MOG autoantibodies pathogenicity in children and macaques demyelinating diseases

17. Targeting MOG to skin macrophages prevents EAE in macaques through TGFβ-induced peripheral tolerance

18. Recombinant Haemagglutinin Derived From the Ciliated Protozoan Tetrahymena thermophila Is Protective Against Influenza Infection

19. Bluetongue Virus Targets Conventional Dendritic Cells in Skin Lymph

20. Delivering HIV Gagp24 to DCIR Induces Strong Antibody Responses $In\ Vivo$

21. HIV specific responses induced in nonhuman primates with ANRS HIV-Lipo-5 vaccine combined with rMVA-HIV prime or boost immunizations

22. Expression of VP7, a Bluetongue virus group specific antigen by viral vectors: Analysis of the induced immune responses and evaluation of protective potential in sheep

23. Canine recombinant adenovirus vector induces an immunogenicity-related gene expression profile in skin-migrated CD11b⁺ -type DCs

24. Unraveling features of the natural MHC class II peptidome of skin-migrated dendritic cells

25. Targeting HIV Gag p24 to DICR on dendritic cells induces T cell and potent and long-lasting antibody responses in non-human primates

26. Canine adenoviruses elicit both humoral and cell-mediated immune responses against rabies following immunisation of sheep

27. The XC chemokine receptor 1 is a conserved selective marker of mammalian cells homologous to mouse CD8alpha+ dendritic cells

28. Bluetongue virus: virology, pathogenesis and immunity

29. Type I interferon producing cells (IPC) can gain lymph nodes via the afferent lymphatic route

30. Hydroxychloroquine use against SARS-CoV-2 infection in non-human primates

31. Non-human primate models of human respiratory infections

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31 results on '"Vanessa Contreras"'

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