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

Jingyun Yang, W. Wang, Zimin Chen, Shuaiyao Lu, Fanli Yang, Zhenfei Bi, L. Bao, Fei Mo, Xue Li, Y. Huang, Weiqi Hong, Yun Yang, Yuan Zhao, F. Ye, Sheng Lin, W. Deng, Hongming Chen, Hong Lei, Ziqi Zhang, Min Luo, Hong Gao, Yue Zheng, Yanqiu Gong, Xiaohua Jiang, Yanfeng Xu, Qi Lv, Dan Li, Manni Wang, Feng-di Li, Shunyi Wang, Guanpeng Wang, Pin Yu, Yajin Qu, Li Yang, H. Deng, A. Tong, Jiong Li, Zhenling Wang, Jinliang Yang, G. Shen, Zhiwei Zhao, Yuhua Li, Jingwen Luo, Hongqi Liu, Wenhai Yu, Mengli Yang, Jingwen Xu, Jun-bin Wang, Haiyan Li, Haixuan Wang, Dexuan Kuang, Panpan Lin, Zhengtao Hu, W. Guo, W. Cheng, Yanlin He, Xiangrong Song, Chong Chen, Zhihong Xue, S. Yao, Lu Chen, Xuelei Ma, Siyuan Chen, M. Gou, Weijin Huang, Youchun Wang, C. Fan, Z. Tian, M. Shi, Fu-Sheng Wang, L. Dai, M. Wu, Gen Li, G. Wang, Yong Peng, Z. Qian, Canhua Huang, J. Lau, Zhenglin Yang, Yuquan Wei, X. Cen, Xiaozhong Peng, C. Qin, K. Zhang, G. Lu, Xiawei Wei

Nature, 2020

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 cells 1 , 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. A recombinant vaccine that targets the receptor-binding domain of the spike protein of SARS-CoV-2 induces a potent antibody response in immunized mice, rabbits and non-human primates, and protects primates from infection with the virus.

Cited by 177 publications.

Field of study: Biology

10.1038/s41586-020-2599-8