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

Jingyun Yang, Wei Wang, Zimin Chen, Shuaiyao Lu, Fanli Yang, Zhenfei Bi, Linlin Bao, Fei Mo, Xue Li, Yong Huang, Weiqi Hong, Yun Yang, Yuan Zhao, Fei Ye, Sheng Lin, Wei Deng, Hua Chen, Hong Lei, Ziqi Zhang, Min Luo, Hong Gao, Yue Zheng, Yanqiu Gong, Xiaohua Jiang, Yanfeng Xu, Qi Lv, Dan Li, Manni Wang, Fengdi Li, Shunyi Wang, Guanpeng Wang, Pin Yu, Yajin Qu, Li Yang, Hongxin Deng, Aiping Tong, Jiong Li, Zhenling Wang, Jinliang Yang, Guobo Shen, Zhiwei Zhao, Yuhua Li, Jingwen Luo, Hongqi Liu, Wenhai Yu, Mengli Yang, Jingwen Xu, Junbin Wang, Haiyan Li, Haixuan Wang, Dexuan Kuang, Panpan Lin, Zhengtao Hu, Wei Guo, Wei Cheng, Yanlin He, Xiangrong Song, Chong Chen, Zhihong Xue, Shaohua Yao, Lu Chen, Xuelei Ma, Siyuan Chen, Maling Gou, Weijin Huang, Youchun Wang, Changfa Fan, Zhixin Tian, Ming Shi, Fu-Sheng Wang, Lunzhi Dai, Min Wu, Gen Li, Guangyu Wang, Yong Peng, Zhiyong Qian, Canhua Huang, Johnson Yiu-Nam Lau, Zhenglin Yang, Yuquan Wei, Xiaobo Cen, Xiaozhong Peng, Chuan Qin, Kang Zhang (), Guangwen Lu () and Xiawei Wei ()
Additional contact information
Jingyun Yang: Sichuan University
Wei Wang: Sichuan University
Zimin Chen: Sichuan University
Shuaiyao Lu: Chinese Academy of Medical Sciences and Peking Union Medical College
Fanli Yang: Sichuan University
Zhenfei Bi: Sichuan University
Linlin Bao: Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Comparative Medicine Center, Peking Union Medical College
Fei Mo: Sichuan University
Xue Li: Sichuan University
Yong Huang: Sichuan University
Weiqi Hong: Sichuan University
Yun Yang: Chinese Academy of Medical Sciences and Peking Union Medical College
Yuan Zhao: Chinese Academy of Medical Sciences and Peking Union Medical College
Fei Ye: Sichuan University
Sheng Lin: Sichuan University
Wei Deng: Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Comparative Medicine Center, Peking Union Medical College
Hua Chen: Sichuan University
Hong Lei: Sichuan University
Ziqi Zhang: Sichuan University
Min Luo: Sichuan University
Hong Gao: Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Comparative Medicine Center, Peking Union Medical College
Yue Zheng: Sichuan University
Yanqiu Gong: Sichuan University
Xiaohua Jiang: Sichuan University
Yanfeng Xu: Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Comparative Medicine Center, Peking Union Medical College
Qi Lv: Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Comparative Medicine Center, Peking Union Medical College
Dan Li: Sichuan University
Manni Wang: Sichuan University
Fengdi Li: Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Comparative Medicine Center, Peking Union Medical College
Shunyi Wang: Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Comparative Medicine Center, Peking Union Medical College
Guanpeng Wang: Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Comparative Medicine Center, Peking Union Medical College
Pin Yu: Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Comparative Medicine Center, Peking Union Medical College
Yajin Qu: Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Comparative Medicine Center, Peking Union Medical College
Li Yang: Sichuan University
Hongxin Deng: Sichuan University
Aiping Tong: Sichuan University
Jiong Li: Sichuan University
Zhenling Wang: Sichuan University
Jinliang Yang: Sichuan University
Guobo Shen: Sichuan University
Zhiwei Zhao: Sichuan University
Yuhua Li: National Institutes for Food and Drug Control (NIFDC)
Jingwen Luo: Sichuan University
Hongqi Liu: Chinese Academy of Medical Sciences and Peking Union Medical College
Wenhai Yu: Chinese Academy of Medical Sciences and Peking Union Medical College
Mengli Yang: Chinese Academy of Medical Sciences and Peking Union Medical College
Jingwen Xu: Chinese Academy of Medical Sciences and Peking Union Medical College
Junbin Wang: Chinese Academy of Medical Sciences and Peking Union Medical College
Haiyan Li: Chinese Academy of Medical Sciences and Peking Union Medical College
Haixuan Wang: Chinese Academy of Medical Sciences and Peking Union Medical College
Dexuan Kuang: Chinese Academy of Medical Sciences and Peking Union Medical College
Panpan Lin: Sichuan University
Zhengtao Hu: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Collaborative Innovation Center for Biotherapy
Wei Guo: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Collaborative Innovation Center for Biotherapy
Wei Cheng: Sichuan University
Yanlin He: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Collaborative Innovation Center for Biotherapy
Xiangrong Song: Sichuan University
Chong Chen: Sichuan University
Zhihong Xue: Sichuan University
Shaohua Yao: Sichuan University
Lu Chen: Sichuan University
Xuelei Ma: Sichuan University
Siyuan Chen: Sichuan University
Maling Gou: Sichuan University
Weijin Huang: National Institutes for Food and Drug Control (NIFDC)
Youchun Wang: National Institutes for Food and Drug Control (NIFDC)
Changfa Fan: National Institutes for Food and Drug Control (NIFDC)
Zhixin Tian: Tongji University
Ming Shi: National Clinical Research Center for Infectious Diseases
Fu-Sheng Wang: National Clinical Research Center for Infectious Diseases
Lunzhi Dai: Sichuan University
Min Wu: Sichuan University
Gen Li: Macau University of Science and Technology
Guangyu Wang: Tsinghua University
Yong Peng: Sichuan University
Zhiyong Qian: Sichuan University
Canhua Huang: Sichuan University
Johnson Yiu-Nam Lau: Hong Kong Polytechnic University
Zhenglin Yang: University of Electronic Science and Technology of China
Yuquan Wei: Sichuan University
Xiaobo Cen: Sichuan University
Xiaozhong Peng: Chinese Academy of Medical Sciences and Peking Union Medical College
Chuan Qin: Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Comparative Medicine Center, Peking Union Medical College
Kang Zhang: Macau University of Science and Technology
Guangwen Lu: Sichuan University
Xiawei Wei: Sichuan University

Nature, 2020, vol. 586, issue 7830, 572-577

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41586-020-2599-8

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