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

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

  • Cell Res. 2022 Mar;32(3):269-287. doi: 10.1038/s41422-022-00612-2.
Zezhong Liu # 1,  Jie Zhou # 1,  Wei Xu # 1,  Wei Deng # 2,  Yanqun Wang # 3 4 5,  Meiyu Wang # 6 7,  Qian Wang 1,  Ming Hsieh 8,  Jingming Dong 8,  Xinling Wang 1,  Weijin Huang 6 7,  Lixiao Xing 1,  Miaoling He 8,  Chunlin Tao 8,  Youhua Xie 1,  Yilong Zhang 9,  Youchun Wang 10 11,  Jincun Zhao 12 13 14,  Zhenghong Yuan 15,  Chuan Qin 16,  Shibo Jiang 17,  Lu Lu 18
Affiliations

Affiliations

  • 1 Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences; Shanghai Institute of Infectious Disease and Biosecurity; Biosafety Level 3 Laboratory, Shanghai Medical College, Shanghai Frontiers Science Center of Pathogenic Microbes and Infection, Fudan University, Shanghai, China.
  • 2 Key Laboratory of Human Disease Comparative Medicine, National Health Commission of the People's Republic of China; Beijing Key Laboratory for Animal Models of Emerging and Reemerging Infectious Diseases, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Comparative Medicine Center, Peking Union Medical College, Beijing, China.
  • 3 State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.
  • 4 Institute of Infectious Disease, Guangzhou Eighth People's Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.
  • 5 Guangzhou Laboratory, Bio-Island, Guangzhou, China.
  • 6 Graduate School of Peking Union Medical College, No. 9 Dongdan Santiao, Dongcheng District, Beijing, China.
  • 7 Division of HIV/AIDS and Sex-transmitted Virus Vaccines, Institute for Biological Product Control, National Institutes for Food and Drug Control (NIFDC), No. 31 Huatuo Street, Daxing District, Beijing, China.
  • 8 Fulgent Pharma LLC., 4978 Santa Anita Avenue, Temple City, CA, USA.
  • 9 Fulgent Pharma LLC., 4978 Santa Anita Avenue, Temple City, CA, USA. [email protected].
  • 10 Graduate School of Peking Union Medical College, No. 9 Dongdan Santiao, Dongcheng District, Beijing, China. [email protected].
  • 11 Division of HIV/AIDS and Sex-transmitted Virus Vaccines, Institute for Biological Product Control, National Institutes for Food and Drug Control (NIFDC), No. 31 Huatuo Street, Daxing District, Beijing, China. [email protected].
  • 12 State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China. [email protected].
  • 13 Institute of Infectious Disease, Guangzhou Eighth People's Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China. [email protected].
  • 14 Guangzhou Laboratory, Bio-Island, Guangzhou, China. [email protected].
  • 15 Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences; Shanghai Institute of Infectious Disease and Biosecurity; Biosafety Level 3 Laboratory, Shanghai Medical College, Shanghai Frontiers Science Center of Pathogenic Microbes and Infection, Fudan University, Shanghai, China. [email protected].
  • 16 Key Laboratory of Human Disease Comparative Medicine, National Health Commission of the People's Republic of China; Beijing Key Laboratory for Animal Models of Emerging and Reemerging Infectious Diseases, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Comparative Medicine Center, Peking Union Medical College, Beijing, China. [email protected].
  • 17 Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences; Shanghai Institute of Infectious Disease and Biosecurity; Biosafety Level 3 Laboratory, Shanghai Medical College, Shanghai Frontiers Science Center of Pathogenic Microbes and Infection, Fudan University, Shanghai, China. [email protected].
  • 18 Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences; Shanghai Institute of Infectious Disease and Biosecurity; Biosafety Level 3 Laboratory, Shanghai Medical College, Shanghai Frontiers Science Center of Pathogenic Microbes and Infection, Fudan University, Shanghai, China. [email protected].
  • # Contributed equally.
PMID: 35046518 DOI: 10.1038/s41422-022-00612-2
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.

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