The emergence of SARS-CoV-2 variants and potentially other highly pathogenic sarbecoviruses in the future highlights the need for pan-sarbecovirus vaccines. Here, we discovered a new STING agonist, CF501, and found that CF501-adjuvanted RBD-Fc vaccine (CF501/RBD-Fc) elicited significantly stronger neutralizing antibody (nAb) and T cell responses than Alum- and cGAMP-adjuvanted RBD-Fc in mice. Vaccination of rabbits and rhesus macaques (nonhuman primates, NHPs) with CF501/RBD-Fc elicited exceptionally potent nAb responses against SARS-CoV-2 and its nine variants and 41 S-mutants, SARS-CoV and bat SARSr-CoVs. CF501/RBD-Fc-immunized hACE2-transgenic mice were almost completely protected against SARS-CoV-2 challenge, even 6 months after the initial immunization. NHPs immunized with a single dose of CF501/RBD-Fc produced high titers of nAbs. The immunized macaques also exhibited durable humoral and cellular immune responses and showed remarkably reduced viral load in the upper and lower airways upon SARS-CoV-2 challenge even at 108 days post the final immunization. Thus, CF501/RBD-Fc can be further developed as a novel pan-sarbecovirus vaccine to combat current and future outbreaks of sarbecovirus diseases.
【저자키워드】 immunology, Molecular biology, Innate immunity, 【초록키워드】 neutralizing antibody, SARS-CoV-2, Vaccine, Diseases, Vaccines, SARS-CoV, Cellular immune response, variant, SARS-CoV-2 variant, immunization, hACE2, T cell, Viral, SARS-CoV-2 variants, Viral load, outbreak, mice, NHPs, immune responses, T cell responses, macaque, T cell response, STING, single dose, NAb, sarbecovirus, rhesus macaques, rhesus macaque, alum, humoral, NAbs, upper and lower airways, CoVs, Final, RBD-Fc, SARSr-CoVs, highly pathogenic, NHP, immunized, highlight, initial, produced, significantly, nine, reduced, exhibited, elicited, responses against, lower airway, 【제목키워드】 Vaccine, T cell response, NHP, elicit,