Volume 32, No 3, Mar 2022

ISSN: 1001-0602 
EISSN: 1748-7838 2018 
impact factor 17.848* 
(Clarivate Analytics, 2019)

Volume 32 Issue 3, March 2022: 269-287   |  Open Access

ORIGINAL ARTICLES

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

Zezhong Liu^1,2,† , Jie Zhou^1,2,† , Wei Xu^1,2,† , Wei Deng^1,2,† , Yanqun Wang^3,4,5,† , Meiyu Wang^6,7,† , Qian Wang^1,2 , Ming Hsieh⁸ , Jingming Dong⁸ , Xinling Wang^1,2 , Weijin Huang^6,7 , Lixiao Xing^1,2 , Miaoling He⁸ , Chunlin Tao⁸ , Youhua Xie^1,2 , Yilong Zhang^8,* , Youchun Wang^6,7,* , Jincun Zhao^3,4,5,* , Zhenghong Yuan^1,2,* , Chuan Qin^1,2 , Shibo Jiang^1,2 , Lu Lu^1,2,*

¹Key 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
²Key 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
³State 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
⁴Institute of Infectious Disease, Guangzhou Eighth People’s Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China
⁵Guangzhou Laboratory, Bio-Island, Guangzhou, China
⁶Graduate School of Peking Union Medical College, No. 9 Dongdan Santiao, Dongcheng District, Beijing, China
⁷Division 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
⁸Fulgent Pharma LLC., 4978 Santa Anita Avenue, Temple City, CA, USA
^†These authors contributed equally: Zezhong Liu, Jie Zhou, Wei Xu, Wei Deng, Yanqun Wang, Meiyu Wang
Correspondence: Yilong Zhang(yilongzhang@fulgentpharma.com)Youchun Wang(wangyc@nifdc.org.cn)Jincun Zhao(zhaojincun@gird.cn)Zhenghong Yuan(zhyuan@shmu.edu.cn)Lu Lu(lul@fudan.edu.cn)

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.

https://doi.org/10.1038/s41422-022-00612-2

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