Cell Reports (Jun 2024)
An unconventional VH1-2 antibody tolerates escape mutations and shows an antigenic hotspot on SARS-CoV-2 spike
- Banghui Liu,
- Xuefeng Niu,
- Yijun Deng,
- Zhaoyong Zhang,
- Yanqun Wang,
- Xijie Gao,
- Huan Liang,
- Zimu Li,
- Qian Wang,
- Yuanyi Cheng,
- Qiuluan Chen,
- Shuangshuang Huang,
- Yingxian Pan,
- Mengzhen Su,
- Xiancheng Lin,
- Chuanying Niu,
- Yinglin Chen,
- Wenyi Yang,
- Yudi Zhang,
- Qihong Yan,
- Jun He,
- Jincun Zhao,
- Ling Chen,
- Xiaoli Xiong
Affiliations
- Banghui Liu
- State Key Laboratory of Respiratory Disease, CAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangdong Provincial Key Laboratory of Biocomputing, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China
- Xuefeng Niu
- 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, China; Corresponding author
- Yijun Deng
- 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, 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, China
- 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, China
- Xijie Gao
- Key Laboratory of Biological Targeting Diagnosis, Therapy and Rehabilitation of Guangdong Higher Education Institutes, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
- Huan Liang
- 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, China
- Zimu Li
- State Key Laboratory of Respiratory Disease, CAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangdong Provincial Key Laboratory of Biocomputing, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China
- Qian Wang
- Guangzhou Laboratory & Bioland Laboratory, Guangzhou, China
- Yuanyi 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, China
- Qiuluan Chen
- Bioland Laboratory (Guangzhou Regenerative Medicine and Health - Guangdong Laboratory), Guangzhou, China
- Shuangshuang Huang
- 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, China
- Yingxian Pan
- 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, China
- Mengzhen Su
- State Key Laboratory of Respiratory Disease, CAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangdong Provincial Key Laboratory of Biocomputing, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China; University of Science and Technology of China, Hefei, China
- Xiancheng Lin
- 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, China
- Chuanying Niu
- State Key Laboratory of Respiratory Disease, CAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangdong Provincial Key Laboratory of Biocomputing, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China; University of Science and Technology of China, Hefei, China
- Yinglin 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, China
- Wenyi Yang
- 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, China
- Yudi Zhang
- State Key Laboratory of Respiratory Disease, CAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangdong Provincial Key Laboratory of Biocomputing, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China; University of Chinese Academy of Sciences, Beijing, 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, China
- Jun He
- State Key Laboratory of Respiratory Disease, CAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangdong Provincial Key Laboratory of Biocomputing, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China
- 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, China; Corresponding author
- Ling Chen
- Guangzhou Laboratory & Bioland Laboratory, Guangzhou, China; Corresponding author
- Xiaoli Xiong
- State Key Laboratory of Respiratory Disease, CAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangdong Provincial Key Laboratory of Biocomputing, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China; Corresponding author
- Journal volume & issue
-
Vol. 43,
no. 6
p. 114265
Abstract
Summary: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein continues to evolve antigenically, impacting antibody immunity. D1F6, an affinity-matured non-stereotypic VH1-2 antibody isolated from a patient infected with the SARS-CoV-2 ancestral strain, effectively neutralizes most Omicron variants tested, including XBB.1.5. We identify that D1F6 in the immunoglobulin G (IgG) form is able to overcome the effect of most Omicron mutations through its avidity-enhanced multivalent S-trimer binding. Cryo-electron microscopy (cryo-EM) and biochemical analyses show that three simultaneous epitope mutations are generally needed to substantially disrupt the multivalent S-trimer binding by D1F6 IgG. Antigenic mutations at spike positions 346, 444, and 445, which appeared in the latest variants, have little effect on D1F6 binding individually. However, these mutations are able to act synergistically with earlier Omicron mutations to impair neutralization by affecting the interaction between D1F6 IgG and the S-trimer. These results provide insight into the mechanism by which accumulated antigenic mutations facilitate evasion of affinity-matured antibodies.
