1区 · 生物学
Article
作者: Qin, Chuan ; Zhou, Jie ; Deng, Wei ; Tao, Chunlin ; Xie, Youhua ; Jiang, Shibo ; Lu, Lu ; Xu, Wei ; Wang, Xinling ; Hsieh, Ming ; Zhang, Yilong ; Wang, Youchun ; Dong, Jingming ; Yuan, Zhenghong ; He, Miaoling ; Xing, Lixiao ; Zhao, Jincun ; Wang, Qian ; Huang, Weijin ; Wang, Yanqun ; Wang, Meiyu ; Liu, Zezhong
Abstract: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.