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

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.
AuthorsJingyun 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, Xiawei Wei
JournalNature (Nature) Vol. 586 Issue 7830 Pg. 572-577 (10 2020) ISSN: 1476-4687 [Electronic] England
PMID32726802 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antibodies, Neutralizing
  • Antibodies, Viral
  • COVID-19 Vaccines
  • Spike Glycoprotein, Coronavirus
  • Viral Vaccines
  • spike protein, SARS-CoV-2
Topics
  • Animals
  • Antibodies, Neutralizing (immunology)
  • Antibodies, Viral (immunology)
  • Betacoronavirus (immunology)
  • COVID-19
  • COVID-19 Vaccines
  • Coronavirus Infections (immunology, prevention & control)
  • Humans
  • Macaca mulatta (immunology, virology)
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Models, Animal
  • Models, Molecular
  • Pandemics (prevention & control)
  • Pneumonia, Viral (immunology, prevention & control)
  • Protein Domains
  • SARS-CoV-2
  • Serum (immunology)
  • Spike Glycoprotein, Coronavirus (chemistry, immunology)
  • Spleen (cytology, immunology)
  • T-Lymphocytes (immunology)
  • Vaccination
  • Viral Vaccines (immunology)

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