A vaccine targeting the RBD of the S protein of SARS-CoV-2 induces protective immunity

Authors

Jingyun Yang, West China School of Medicine/West China Hospital of Sichuan University
Wei Wang, West China School of Medicine/West China Hospital of Sichuan University
Zimin Chen, West China School of Medicine/West China Hospital of Sichuan University
Shuaiyao Lu, Chinese Academy of Medical Sciences & Peking Union Medical College
Fanli Yang, West China School of Medicine/West China Hospital of Sichuan University
Zhenfei Bi, West China School of Medicine/West China Hospital of Sichuan University
Linlin Bao, Ministry of Health of People's Republic of China
Fei Mo, West China School of Medicine/West China Hospital of Sichuan University
Xue Li, West China School of Medicine/West China Hospital of Sichuan University
Yong Huang, West China School of Medicine/West China Hospital of Sichuan University
Weiqi Hong, West China School of Medicine/West China Hospital of Sichuan University
Yun Yang, Chinese Academy of Medical Sciences & Peking Union Medical College
Yuan Zhao, Chinese Academy of Medical Sciences & Peking Union Medical College
Fei Ye, West China School of Medicine/West China Hospital of Sichuan University
Sheng Lin, West China School of Medicine/West China Hospital of Sichuan University
Wei Deng, Ministry of Health of People's Republic of China
Hua Chen, West China School of Medicine/West China Hospital of Sichuan University
Hong Lei, West China School of Medicine/West China Hospital of Sichuan University
Ziqi Zhang, West China School of Medicine/West China Hospital of Sichuan University
Min Luo, West China School of Medicine/West China Hospital of Sichuan University
Hong Gao, Ministry of Health of People's Republic of China
Yue Zheng, West China School of Medicine/West China Hospital of Sichuan University
Yanqiu Gong, West China School of Medicine/West China Hospital of Sichuan University
Xiaohua Jiang, West China School of Medicine/West China Hospital of Sichuan University
Yanfeng Xu, Ministry of Health of People's Republic of China
Qi Lv, Ministry of Health of People's Republic of China
Dan Li, West China School of Medicine/West China Hospital of Sichuan University
Manni Wang, West China School of Medicine/West China Hospital of Sichuan University
Fengdi Li, Ministry of Health of People's Republic of China
Shunyi Wang, Ministry of Health of People's Republic of China
Guanpeng Wang, Ministry of Health of People's Republic of China
Pin Yu, Ministry of Health of People's Republic of China
Yajin Qu, Ministry of Health of People's Republic of China
Li Yang, West China School of Medicine/West China Hospital of Sichuan University

Document Type

Article

Publication Date

10-22-2020

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a respiratory disease called coronavirus disease 2019 (COVID-19), the spread of which has led to a pandemic. An effective preventive vaccine against this virus is urgently needed. As an essential step during infection, SARS-CoV-2 uses the receptor-binding domain (RBD) of the spike protein to engage with the receptor angiotensin-converting enzyme 2 (ACE2) on host cells1,2. Here we show that a recombinant vaccine that comprises residues 319–545 of the RBD of the spike protein induces a potent functional antibody response in immunized mice, rabbits and non-human primates (Macaca mulatta) as early as 7 or 14 days after the injection of a single vaccine dose. The sera from the immunized animals blocked the binding of the RBD to ACE2, which is expressed on the cell surface, and neutralized infection with a SARS-CoV-2 pseudovirus and live SARS-CoV-2 in vitro. Notably, vaccination also provided protection in non-human primates to an in vivo challenge with SARS-CoV-2. We found increased levels of RBD-specific antibodies in the sera of patients with COVID-19. We show that several immune pathways and CD4 T lymphocytes are involved in the induction of the vaccine antibody response. Our findings highlight the importance of the RBD domain in the design of SARS-CoV-2 vaccines and provide a rationale for the development of a protective vaccine through the induction of antibodies against the RBD domain.

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