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

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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

Edité par CCSD ; Cell Press -

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.

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