The SARS-CoV-2 pandemic causes an ongoing global health crisis, which requires efficient and safe vaccination programs. In this study, researchers at the IBS (EBEV, CAID, MEM et M&P groups), in collaboration with IDMIT, Amsterdam University and Institut Pasteur, develop synthetic SARS-CoV2 S glycoprotein-coated liposomes that resemble virus-like particles. Soluble S glycoprotein trimers were stabilized by formaldehyde cross-linking and coated onto lipid vesicles (S-VLP). Immunization of cynomolgus macaques with the S-VLP nanoparticles induced high antibody titers with potent neutralizing activity against the vaccine strain, Alpha, Beta, and Gamma variants and TH1 CD4+ biased T cell responses.Upon the first and second immunization, antibodies were most mostly generated against the receptor binding domain (RBD), which is immunodominant, while the third immunization boosted non-RBD antibody titers. Sera from immunized animals showed potent neutralization against the vaccine strain and the Alpha variant after two immunizations and robust neutralization of Beta and Gamma strains after teh third immunization. Challenge of animals with SARS-CoV-2 shows a complete protection through sterilizing immunity, which may correlate with the detectio of mucosal immune antibody titers.
Thus, the S-VLP nanoparticle vaccine candidate is efficient and safe, based on a proven classical approach for further development and clinical testing.
Immunization with synthetic SARS-CoV-2 S glycoprotein virus-like particles protects Macaques from infection. Guidenn Sulbaran, Pauline Maisonnasse, Axelle Amen, Gregory Effantin, Delphine Guilligay, Nathalie Dereuddre-Bosquet, Judith A. Burger, Meliawati Poniman, Marlyse Buisson, Sebastian Dergan Dylon, Thibaut Naninck, Julien Lemaître, Wesley Gros, Anne-Sophie Gallouët, Romain Marlin, Camille Bouillier, Vanessa Contreras, Francis Relouzat, Daphna Fenel, Michel Thepaut, Isabelle Bally, Nicole Thielens, Franck Fieschi, Guy Schoehn, Sylvie van der Werf, View ORCID ProfileMarit J. van Gils, Rogier W. Sanders, Pascal Poignard, Roger Le Grand, Winfried Weissenhorn. Cell Reports Medicine doi : 10.1016/j.xcrm.2022.100528
Contact : Winfried Weissenhorn (IBS/Entry and Budding of Enveloped Viruses group)