Identification of a broad sarbecovirus neutralizing antibody targeting a conserved epitope on the receptor-binding domain

Wang，Yanqun1,2,3; Zhang，Zhaoyong1; Yang，Minnan4; Xiong，Xinyi5; Yan，Qihong1; Cao，Lei4; Wei，Peilan1,6; Zhang，Yuting1; Zhang，Lu7; Lv，Kexin8; Chen，Jiantao1; Liu，Xuesong9; Zhao，Xiaochu10; Xiao，Juxue1; Zhang，Shengnan1; Zhu，Airu1; Gan，Mian1; Zhang，Jingjun1; Cai，Ruoxi1; Zhuo，Jianfen1; Zhang，Yanjun1; Rao，Haiyue1; Qu，Bin5; Zhang，Yuanyuan1; Chen，Lei1; Dai，Jun7; Cheng，Linling1; Hu，Qingtao1; Chen，Yaoqing8; Lv，Huibin11; So，Ray T.Y.12; Peiris，Malik11,12; Zhao，Jingxian1,6; Liu，Xiaoqing9; Mok，Chris Ka Pun13,14,16; Wang，Xiangxi4; Zhao，Jincun1,5,6,15

2024-01-23

10.1016/j.celrep.2023.113653

Cell Reports   影响因子和分区

2211-1247

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.

conserved epitope CP: Immunology in vivo mouse model neutralizing antibody receptor binding domain sarbecovirus

SCI

英语

其他

2-s2.0-85181812865

Scopus

1.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
2.GMU-GIBH Joint School of Life Sciences,Guangzhou Medical University,Guangzhou,Guangdong,China
3.Clinical Laboratory Medicine Department,The Second Affiliated Hospital of Guangzhou Medical University,Guangzhou,China
4.CAS Key Laboratory of Infection and Immunity,National Laboratory of Macromolecules,Institute of Biophysics,Chinese Academy of Sciences,Beijing,China
5.Shanghai Institute for Advanced Immunochemical Studies,School of Life Science and Technology,ShanghaiTech University,Shanghai,China
6.Guangzhou National Laboratory,Bio-Island,Guangzhou,China
7.Health and Quarantine Laboratory,Guangzhou Customs District Technology Centre,Guangzhou,China
8.School of Public Health (Shenzhen),Sun Yat-sen University,Shenzhen,China
9.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
10.School of Basic Medical Sciences,Capital Medical University,Beijing,China
11.HKU-Pasteur Research Pole,School of Public Health,Li Ka Shing Faculty of Medicine,The University of Hong Kong,Hong Kong,Hong Kong
12.School of Public Health,The University of Hong Kong,Hong Kong,Hong Kong
13.The Jockey Club School of Public Health and Primary Care,The Chinese University of Hong Kong,Hong Kong,Hong Kong
14.Li Ka Shing Institute of Health Sciences,Faculty of Medicine,The Chinese University of Hong Kong,Hong Kong,Hong Kong
15.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
16.S.H. Ho Research Centre for Infectious Diseases,Chinese University of Hong Kong,Hong Kong,Hong Kong

Wang，Yanqun,Zhang，Zhaoyong,Yang，Minnan,et al. Identification of a broad sarbecovirus neutralizing antibody targeting a conserved epitope on the receptor-binding domain[J]. Cell Reports,2024,43(1).

Wang，Yanqun.,Zhang，Zhaoyong.,Yang，Minnan.,Xiong，Xinyi.,Yan，Qihong.,...&Zhao，Jincun.(2024).Identification of a broad sarbecovirus neutralizing antibody targeting a conserved epitope on the receptor-binding domain.Cell Reports,43(1).

Wang，Yanqun,et al."Identification of a broad sarbecovirus neutralizing antibody targeting a conserved epitope on the receptor-binding domain".Cell Reports 43.1(2024).