Immunization with synthetic SARS-CoV-2 S glycoprotein virus-like particles protects Macaques from infection

Sulbaran, Guidenn; Maisonnasse, Pauline; Amen, Axelle; Guilligay, Delphine; Dereuddre-Bosquet, Nathalie; Burger, Judith A.; Poniman, Meliawati; 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 J.; Sanders, Rogier W.; Poignard, Pascal; Le Grand, Roger; Weissenhorn, Winfried

The SARS-CoV-2 pandemic causes an ongoing global health crisis, which requires efficient and safe vaccination programs. Here, we present synthetic SARS-CoV2 S glycoprotein-coated liposomes that resemble in size and surface structure 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 S-VLPs induced high antibody titers and TH1 CD4+ biased T cell responses. Although antibody responses were initially dominated by RBD specificity, the third immunization boosted non-RBD antibody titers. Antibodies showed potent neutralization against the vaccine strain and the Alpha variant after two immunizations and robust neutralization of Beta and Gamma strains. Challenge of animals with SARS-CoV-2 protected all vaccinated animals by sterilizing immunity. Thus, the S-VLP approach is an efficient and safe vaccine candidate based on a proven classical approach for further development and clinical testing.