Abstract
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.
Keywords: B cells; COVID-19; S glycoprotein; SARS-CoV-2; antibodies; formaldehyde cross-linking; immunity; macaques; nanoparticles; protection.
【저자키워드】 COVID-19, antibodies, SARS-CoV-2, Immunity, B cells, Nanoparticles, S glycoprotein, formaldehyde cross-linking, macaques, protection., 【초록키워드】 IgG, coronavirus, pandemic, Antibody Response, variant, B cells, severe acute respiratory syndrome Coronavirus, CD4, immunization, Health crisis, Neutralizing activity, T cell, Immunoglobulin G, Health, Receptor-binding domain, Immunoglobulin, sterilizing immunity, nasopharyngeal, T cell responses, Antibody titer, Gamma, vaccine candidate, Alpha, Beta, respiratory, virus-like particles, Antibody titers, boost, cynomolgus macaques, SARS-CoV-2 spike, S glycoprotein, macaques, cynomolgus macaque, Safe, formaldehyde, T helper, acute respiratory syndrome, acute respiratory syndrome coronavirus, acute respiratory syndrome coronavirus 2, anti-receptor-binding domain, trimer, clinical testing, anti-S, receptor-binding domains, vaccine strain, IgA titers, Complete, Vesicle, approach, classical, caused, induce, coated, the vaccine, predominant, 【제목키워드】 Infection, macaque, S glycoprotein, Virus-like particle, SARS-CoV-2 S glycoprotein, PROTECT,