Abstract
Original language | English |
---|---|
Article number | 100528 |
Journal | Cell Reports Medicine |
Volume | 3 |
Issue number | 2 |
Early online date | 2022 |
DOIs | |
Publication status | Published - 15 Feb 2022 |
Keywords
- B cells
- COVID-19
- S glycoprotein
- SARS-CoV-2
- antibodies
- formaldehyde cross-linking
- immunity
- macaques
- nanoparticles
- protection
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In: Cell Reports Medicine, Vol. 3, No. 2, 100528, 15.02.2022.
Research output: Contribution to journal › Article › Academic › peer-review
TY - JOUR
T1 - Immunization with synthetic SARS-CoV-2 S glycoprotein virus-like particles protects macaques from infection
AU - Sulbaran, Guidenn
AU - Maisonnasse, Pauline
AU - Amen, Axelle
AU - Effantin, Gregory
AU - Guilligay, Delphine
AU - Dereuddre-Bosquet, Nathalie
AU - Burger, Judith A.
AU - Poniman, Meliawati
AU - Grobben, Marloes
AU - Buisson, Marlyse
AU - Dergan Dylon, Sebastian
AU - Naninck, Thibaut
AU - Lemaître, Julien
AU - Gros, Wesley
AU - Gallouët, Anne-Sophie
AU - Marlin, Romain
AU - Bouillier, Camille
AU - Contreras, Vanessa
AU - Relouzat, Francis
AU - Fenel, Daphna
AU - Thepaut, Michel
AU - Bally, Isabelle
AU - Thielens, Nicole
AU - Fieschi, Franck
AU - Schoehn, Guy
AU - van der Werf, Sylvie
AU - van Gils, Marit J.
AU - Sanders, Rogier W.
AU - Poignard, Pascal
AU - le Grand, Roger
AU - Weissenhorn, Winfried
N1 - Funding Information: 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). The funders had no role in study design, data collection, data analysis, data interpretation, or data reporting. Funding Information: 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 M?dicale (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). The funders had no role in study design, data collection, data analysis, data interpretation, or data reporting. We thank J. McLellan for providing the S expression vector; B. Delache, E. Burban, J. Demilly, N. Dhooge, S. Langlois, P. Le Calvez, Q. Sconosciuti, V. Magneron, M. Rimlinger, A. Berriche, J.H. Qiu, M. Potier, J.M. Robert, and C. Dodan for help with animal studies and R. Ho Tsong Fang for his supervision; L. Bossevot, M. Leonec, L. Moenne-Loccoz, and J. Morin for the qRT-PCR and preparation of reagents; M. Gomez-Pacheco and J. van Wassenhove for cellular assays; N. Kahlaoui, B. Fert, and C. Mayet for help with the CT scans and C. Chapon for her supervision; M. Barendji, J. Dinh, and E. Guyon for the NHP sample processing; S. Keyser for the transports organization; F. Ducancel and Y. Gorin for their help with the logistics and safety management; and I. Mangeot for her help with resource management. We thank Antoine Nougairede for sharing the plasmid used for the sgRNA assay standardization. Finally, we thank Dietmar Katinger and Philipp Mundsperger (Polymun) for providing MPLA liposomes. Images in Figures 2A and S1F and the graphical abstract were created with BioRender.com. Conceptualization, W.W. G.S. R.L.G. and P.M.; funding acquisition, W.W. R.L.G. and R.W.S.; investigation, G.S. P.M. A.A. G.E. D.G. J.A.B. M.P. M.G. M.B. S.D.D. T.N. J.L. W.G. A.-S.G. R.M. C.B. V.C. F.R. and D.F.; methodology, G.S. W.W. P.M. M.J.v.G. R.W.S. P.P. and R.L.G.; formal analyses, G.S. P.M. A.A. N.D.-B. S.D.D. T.N. and A.-S.G.; resources, M.T. I.B. N.T. F.F. N.D.-B. and S.v.d.W.; visualization: G.S. P.M. and G.E.; supervision, W.W. R.L.G. N.D.-B. G.S. M.J.v.G. R.W.S, and P.P.; writing ? original draft, W.W. P.M. G.S. and R.L.G.; writing ? review & editing, all authors. The authors declare no competing interests. Publisher Copyright: © 2022 The Authors
PY - 2022/2/15
Y1 - 2022/2/15
N2 - 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.
AB - 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.
KW - B cells
KW - COVID-19
KW - S glycoprotein
KW - SARS-CoV-2
KW - antibodies
KW - formaldehyde cross-linking
KW - immunity
KW - macaques
KW - nanoparticles
KW - protection
UR - http://www.scopus.com/inward/record.url?scp=85124049454&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.xcrm.2022.100528
DO - https://doi.org/10.1016/j.xcrm.2022.100528
M3 - Article
C2 - 35233549
SN - 2666-3791
VL - 3
JO - Cell Reports Medicine
JF - Cell Reports Medicine
IS - 2
M1 - 100528
ER -