Cell Reports (Jan 2024)
Identification of a broad sarbecovirus neutralizing antibody targeting a conserved epitope on the receptor-binding domain
- Yanqun Wang,
- Zhaoyong Zhang,
- Minnan Yang,
- Xinyi Xiong,
- Qihong Yan,
- Lei Cao,
- Peilan Wei,
- Yuting Zhang,
- Lu Zhang,
- Kexin Lv,
- Jiantao Chen,
- Xuesong Liu,
- Xiaochu Zhao,
- Juxue Xiao,
- Shengnan Zhang,
- Airu Zhu,
- Mian Gan,
- Jingjun Zhang,
- Ruoxi Cai,
- Jianfen Zhuo,
- Yanjun Zhang,
- Haiyue Rao,
- Bin Qu,
- Yuanyuan Zhang,
- Lei Chen,
- Jun Dai,
- Linling Cheng,
- Qingtao Hu,
- Yaoqing Chen,
- Huibin Lv,
- Ray T.Y. So,
- Malik Peiris,
- Jingxian Zhao,
- Xiaoqing Liu,
- Chris Ka Pun Mok,
- Xiangxi Wang,
- Jincun Zhao
Affiliations
- Yanqun Wang
- State 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; GMU-GIBH Joint School of Life Sciences, Guangzhou Medical University, Guangzhou, Guangdong, China; Clinical Laboratory Medicine Department, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
- Zhaoyong Zhang
- State 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
- Minnan Yang
- CAS Key Laboratory of Infection and Immunity, National Laboratory of Macromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China
- Xinyi Xiong
- Shanghai Institute for Advanced Immunochemical Studies, School of Life Science and Technology, ShanghaiTech University, Shanghai, China
- Qihong Yan
- State 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
- Lei Cao
- CAS Key Laboratory of Infection and Immunity, National Laboratory of Macromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China
- Peilan Wei
- State 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; Guangzhou National Laboratory, Bio-Island, Guangzhou, China
- Yuting Zhang
- State 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
- Lu Zhang
- Health and Quarantine Laboratory, Guangzhou Customs District Technology Centre, Guangzhou, China
- Kexin Lv
- School of Public Health (Shenzhen), Sun Yat-sen University, Shenzhen, China
- Jiantao Chen
- State 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
- Xuesong Liu
- Department of Critical Care Medicine, State Key Lab of Respiratory Diseases, Guangzhou Institute of Respiratory Health, National Clinical Research Center for Respiratory Disease, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
- Xiaochu Zhao
- School of Basic Medical Sciences, Capital Medical University, Beijing, China
- Juxue Xiao
- State 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
- Shengnan Zhang
- State 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
- Airu Zhu
- State 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
- Mian Gan
- State 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
- Jingjun Zhang
- State 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
- Ruoxi Cai
- State 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
- Jianfen Zhuo
- State 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
- Yanjun Zhang
- State 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
- Haiyue Rao
- State 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
- Bin Qu
- Shanghai Institute for Advanced Immunochemical Studies, School of Life Science and Technology, ShanghaiTech University, Shanghai, China
- Yuanyuan Zhang
- State 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
- Lei Chen
- State 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
- Jun Dai
- Health and Quarantine Laboratory, Guangzhou Customs District Technology Centre, Guangzhou, China
- Linling Cheng
- State 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
- Qingtao Hu
- State 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
- Yaoqing Chen
- School of Public Health (Shenzhen), Sun Yat-sen University, Shenzhen, China
- Huibin Lv
- HKU-Pasteur Research Pole, School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
- Ray T.Y. So
- School of Public Health, The University of Hong Kong, Hong Kong, China
- Malik Peiris
- HKU-Pasteur Research Pole, School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China; School of Public Health, The University of Hong Kong, Hong Kong, China
- Jingxian Zhao
- State 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; Guangzhou National Laboratory, Bio-Island, Guangzhou, China
- Xiaoqing Liu
- Department of Critical Care Medicine, State Key Lab of Respiratory Diseases, Guangzhou Institute of Respiratory Health, National Clinical Research Center for Respiratory Disease, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China; Corresponding author
- Chris Ka Pun Mok
- The Jockey Club School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong, China; Li Ka Shing Institute of Health Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China; Corresponding author
- Xiangxi Wang
- CAS Key Laboratory of Infection and Immunity, National Laboratory of Macromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China; Corresponding author
- Jincun Zhao
- State 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; Shanghai Institute for Advanced Immunochemical Studies, School of Life Science and Technology, ShanghaiTech University, Shanghai, China; Guangzhou National Laboratory, Bio-Island, Guangzhou, China; Institute for Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People’s Hospital, the Second Affiliated Hospital, School of Medicine, Southern University of Science and Technology, Shenzhen, China; Corresponding author
- Journal volume & issue
-
Vol. 43,
no. 1
p. 113653
Abstract
Summary: Omicron, as the emerging variant with enhanced vaccine tolerance, has sharply disrupted most therapeutic antibodies. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) belongs to the subgenus Sarbecovirus, members of which share high sequence similarity. Herein, we report one sarbecovirus antibody, 5817, which has broad-spectrum neutralization capacity against SARS-CoV-2 variants of concern (VOCs) and SARS-CoV, as well as related bat and pangolin viruses. 5817 can hardly compete with six classes of receptor-binding-domain-targeted antibodies grouped by structural classifications. No obvious impairment in the potency is detected against SARS-CoV-2 Omicron and subvariants. The cryoelectron microscopy (cryo-EM) structure of neutralizing antibody 5817 in complex with Omicron spike reveals a highly conserved epitope, only existing at the receptor-binding domain (RBD) open state. Prophylactic and therapeutic administration of 5817 potently protects mice from SARS-CoV-2 Beta, Delta, Omicron, and SARS-CoV infection. This study reveals a highly conserved cryptic epitope targeted by a broad sarbecovirus neutralizing antibody, which would be beneficial to meet the potential threat of pre-emergent SARS-CoV-2 VOCs.
