| Title: |
Immunization with synthetic SARS-CoV-2 S glycoprotein virus-like particles protects macaques from infection |
| Authors: |
Sulbaran, Guidenn; Maisonnasse, Pauline; Amen, Axelle; Effantin, Gregory; Guilligay, Delphine; Dereuddre-Bosquet, Nathalie; Burger, Judith; Poniman, Meliawati; Grobben, Marloes; Buisson, Marlyse; Dergan Dylon, Sebastian; Naninck, Thibaut; Lemaître, Julien; Gros, Wesley; Gallouët, Anne-Sophie; Marlin, Romain; Bouillier, Camille; Contreras, Vanessa; Relouzat, Francis; Fenel, Daphna; Thepaut, Michel; Bally, Isabelle; Thielens, Nicole; Fieschi, Franck; Schoehn, Guy; van Der Werf, Sylvie; van Gils, Marit; Sanders, Rogier; Poignard, Pascal; Le Grand, Roger; Weissenhorn, Winfried |
| Contributors: |
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; Universiteit van Amsterdam = University of 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 - laboratoire coordonnateur); 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-PHC-2014-2015,H2020-PHC-2015-single-stage_RTD,EHVA(2016); European Project: 730964,H2020-INFRAIA-2016-2017,H2020-INFRAIA-2016-1,TRANSVAC2(2017); European Project: 653316,H2020-INFRAIA-2014-2015,H2020-INFRAIA-2014-2015,EVAg(2015) |
| Source: |
ISSN: 2666-3791 ; Cell Reports Medicine ; https://hal.univ-grenoble-alpes.fr/hal-03621344 ; Cell Reports Medicine, 2022, 3 (2), pp.100528. ⟨10.1016/j.xcrm.2022.100528⟩. |
| Publisher Information: |
CCSD; Cell Press |
| Publication Year: |
2022 |
| Subject Terms: |
nanoparticles; macaques; immunity; formaldehyde cross-linking; antibodies; SARS-CoV-2; S glycoprotein; COVID-19; protection; B cells; MESH: Animals; MESH: Antibodies; Neutralizing; MESH: Disease Models; Animal; MESH: HEK293 Cells; MESH: Immunoglobulin G; MESH: Humans; MESH: Immunoglobulin A; MESH: Liposomes; MESH: Macaca fascicularis; MESH: Male; MESH: Pandemics; MESH: SARS-CoV-2; MESH: Treatment Outcome; MESH: Spike Glycoprotein; Coronavirus; MESH: Th1 Cells; MESH: Vaccination; Viral |
| Description: |
International audience ; 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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/35233549; info:eu-repo/grantAgreement//681032/EU/European HIV Vaccine Alliance (EHVA): a EU platform for the discovery and evaluation of novel prophylactic and therapeutic vaccine candidates/EHVA; info:eu-repo/grantAgreement//730964/EU/European Vaccine Research and Development Infrastructure/TRANSVAC2; info:eu-repo/grantAgreement//653316/EU/European Virus Archive goes global/EVAg; PUBMED: 35233549; PUBMEDCENTRAL: PMC8784613 |
| DOI: |
10.1016/j.xcrm.2022.100528 |
| Availability: |
https://hal.univ-grenoble-alpes.fr/hal-03621344; https://hal.univ-grenoble-alpes.fr/hal-03621344v1/document; https://hal.univ-grenoble-alpes.fr/hal-03621344v1/file/1-s2.0-S2666379122000283-main.pdf; https://doi.org/10.1016/j.xcrm.2022.100528 |
| Rights: |
http://creativecommons.org/licenses/by-nc-nd/ ; info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.E91FA8DA |
| Database: |
BASE |