Immunization with synthetic SARS-CoV-2 S glycoprotein virus-like particles protects macaques from infection
| Autor: | 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 |
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| Přispěvatelé: | 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, UMS 3518 CNRS-CEA-UGA-EMBL) |
| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
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 |
| Zdroj: | Cell Reports Medicine Cell Reports Medicine, 2022, 3 (2), pp.100528. ⟨10.1016/j.xcrm.2022.100528⟩ Cell Reports Medicine, 3(2):100528. Cell Press |
| ISSN: | 2666-3791 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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