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：Liu, Zezhong; Zhou, Jie; Xu, Wei; Deng, Wei; Wang, Yanqun; Wang, Meiyu; Wang, Qian; Hsieh, Ming; Dong, Jingming; Wang, Xinling; Huang, Weijin; Xing, Lixiao; He, Miaoling; Tao, Chunlin; Xie, Youhua; Zhang, Yilong; Wang, Youchun; Zhao, Jincun; Yuan, Zhenghong^*; Qin, Chuan^*; Jiang, Shibo^*; Lu, Lu^*

来源：Cell Research, 2022, 32(3): 269-287.

DOI：10.1038/s41422-022-00612-2

• RECEPTOR-BINDING DOMAIN
• CORONAVIRUS SPIKE PROTEIN
• CYCLIC GMP-AMP
• NANOPARTICLE VACCINES
• SARS-COV-2 SPIKE
• SARS-COV
• COVID-19
• INFECTION
• IMMUNITY
• DESIGN

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.

• 单位
  中国医学科学院北京协和医院; 复旦大学; 1; 广州医学院