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

• Published in: Cell research Vol. 32; no. 3; pp. 269 - 287
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01.03.2022; Springer Singapore
• Subjects: Agonists; Animals; Antibodies; Antibodies, Neutralizing; Antibodies, Viral; COVID-19 - prevention & control; COVID-19 Vaccines; Immune response (cell-mediated); Immune response (humoral); Immunization; Lymphocytes; Lymphocytes T; Macaca mulatta; Mice; Neutralizing; Rabbits; SARS-CoV-2; Severe acute respiratory syndrome; Severe acute respiratory syndrome coronavirus 2; Spike Glycoprotein, Coronavirus; T-Lymphocytes; Transgenic mice; Vaccines; Viral diseases
• ISSN: 1001-0602; 1748-7838
• DOI: 10.1038/s41422-022-00612-2

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.