ABSTRACT
The SARS-CoV-2 pandemic causes an ongoing global health crisis. Here, we present as a vaccine candidate synthetic SARS-CoV2 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 which keeps all receptor binding domains in the “down” conformation. Immunization of cynomolgus macaques with S coated onto lipid vesicles (S-LV) induces high antibody titers with potent neutralizing activity against the vaccine strain, alpha, beta and gamma variants as well as TH1 CD4+ biased T cell responses. Although anti-RBD specific antibody responses are initially predominant, the third immunization boosts significant non-RBD antibody titers. Challenging of vaccinated animals with SARS-CoV-2 shows complete protection through sterilizing immunity, which correlates with the presence of nasopharyngeal anti-S 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.
Fuente: Cell Reports Medicine
