A novel STING agonist-adjuvanted pan-sarbecovirus vaccine elicits potent and durable neutralizing antibody and T cell responses in mice,rabbits and NHPs

• 作者: Zezhong Liu Jie Zhou Wei Xu Wei Deng Yanqun Wang Meiyu Wang Qian Wang Ming Hsieh Jingming Dong Xinling Wang Weijin Huangei Lixiao Xing Miaoling He Chunlin Tao Youhua Xie Yilong Zhang Youchun Wang Jincun Zhao Zhenghong Yuan Chuan Qin Shibo Jiang Lu Lu
• 来源期刊: 细胞研究（英文版）
• 年，卷（期）: 2022,（3）
• 所属期刊栏目: ARTICLES
• 页码范围: 269-287
• 页数: 19页
• 语种: 英文

摘要

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.