Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Comprehensive Epitope Mapping of Broad Sarbecovirus Neutralizing Antibodies

Yunlong Cao, Ayijiang Yisimayi, Fanchong Jian, Tianhe Xiao, Weiliang Song, View ORCID ProfileJing Wang, Shuo Du, Zhiying Zhang, Pulan Liu, Xiaohua Hao, Qianqian Li, Peng Wang, Ran An, Yao Wang, Jing Wang, Haiyan Sun, Lijuan Zhao, Wen Zhang, Dong Zhao, Jiang Zheng, Lingling Yu, Can Li, Na Zhang, Rui Wang, Xiao Niu, Sijie Yang, Xuetao Song, Linlin Zheng, Zhiqiang Li, Qingqing Gu, Fei Shao, Weijin Huang, Youchun Wang, Ronghua Jin, Junyu Xiao, Xiaoliang Sunney Xie
doi: https://doi.org/10.1101/2022.02.07.479349
Yunlong Cao
1Changping Laboratory, Beijing, P.R. China
2Biomedical Pioneering Innovation Center (BIOPIC), Peking University, Beijing, P.R. China
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: yunlongcao@pku.edu.cn ronghuajin@ccmu.edu.cn junyuxiao@pku.edu.cn sunneyxie@biopic.pku.edu.cn
Ayijiang Yisimayi
2Biomedical Pioneering Innovation Center (BIOPIC), Peking University, Beijing, P.R. China
3School of Life Sciences, Peking University, Beijing, P.R. China
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Fanchong Jian
2Biomedical Pioneering Innovation Center (BIOPIC), Peking University, Beijing, P.R. China
4Joint Graduate Program of Peking-Tsinghua-NIBS, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Tianhe Xiao
2Biomedical Pioneering Innovation Center (BIOPIC), Peking University, Beijing, P.R. China
5College of Chemistry and Molecular Engineering, Peking University, Beijing, P.R. China
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Weiliang Song
2Biomedical Pioneering Innovation Center (BIOPIC), Peking University, Beijing, P.R. China
3School of Life Sciences, Peking University, Beijing, P.R. China
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jing Wang
2Biomedical Pioneering Innovation Center (BIOPIC), Peking University, Beijing, P.R. China
3School of Life Sciences, Peking University, Beijing, P.R. China
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Jing Wang
Shuo Du
3School of Life Sciences, Peking University, Beijing, P.R. China
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Zhiying Zhang
3School of Life Sciences, Peking University, Beijing, P.R. China
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Pulan Liu
3School of Life Sciences, Peking University, Beijing, P.R. China
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Xiaohua Hao
6Beijing Ditan Hospital, Capital Medical University, Beijing, P.R. China
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Qianqian Li
7Division of HIV/AIDS and Sex-transmitted Virus Vaccines, Institute for Biological Product Control, National Institutes for Food and Drug Control (NIFDC), Beijing, P.R. China
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Peng Wang
1Changping Laboratory, Beijing, P.R. China
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ran An
2Biomedical Pioneering Innovation Center (BIOPIC), Peking University, Beijing, P.R. China
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yao Wang
1Changping Laboratory, Beijing, P.R. China
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jing Wang
1Changping Laboratory, Beijing, P.R. China
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Haiyan Sun
1Changping Laboratory, Beijing, P.R. China
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Lijuan Zhao
1Changping Laboratory, Beijing, P.R. China
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Wen Zhang
6Beijing Ditan Hospital, Capital Medical University, Beijing, P.R. China
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Dong Zhao
6Beijing Ditan Hospital, Capital Medical University, Beijing, P.R. China
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jiang Zheng
1Changping Laboratory, Beijing, P.R. China
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Lingling Yu
1Changping Laboratory, Beijing, P.R. China
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Can Li
1Changping Laboratory, Beijing, P.R. China
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Na Zhang
1Changping Laboratory, Beijing, P.R. China
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Rui Wang
1Changping Laboratory, Beijing, P.R. China
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Xiao Niu
2Biomedical Pioneering Innovation Center (BIOPIC), Peking University, Beijing, P.R. China
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sijie Yang
2Biomedical Pioneering Innovation Center (BIOPIC), Peking University, Beijing, P.R. China
8Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, P.R. China
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Xuetao Song
1Changping Laboratory, Beijing, P.R. China
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Linlin Zheng
1Changping Laboratory, Beijing, P.R. China
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Zhiqiang Li
8Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, P.R. China
9Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, P.R. China
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Qingqing Gu
1Changping Laboratory, Beijing, P.R. China
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Fei Shao
1Changping Laboratory, Beijing, P.R. China
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Weijin Huang
7Division of HIV/AIDS and Sex-transmitted Virus Vaccines, Institute for Biological Product Control, National Institutes for Food and Drug Control (NIFDC), Beijing, P.R. China
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Youchun Wang
7Division of HIV/AIDS and Sex-transmitted Virus Vaccines, Institute for Biological Product Control, National Institutes for Food and Drug Control (NIFDC), Beijing, P.R. China
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ronghua Jin
6Beijing Ditan Hospital, Capital Medical University, Beijing, P.R. China
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: yunlongcao@pku.edu.cn ronghuajin@ccmu.edu.cn junyuxiao@pku.edu.cn sunneyxie@biopic.pku.edu.cn
Junyu Xiao
3School of Life Sciences, Peking University, Beijing, P.R. China
8Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, P.R. China
9Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, P.R. China
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: yunlongcao@pku.edu.cn ronghuajin@ccmu.edu.cn junyuxiao@pku.edu.cn sunneyxie@biopic.pku.edu.cn
Xiaoliang Sunney Xie
1Changping Laboratory, Beijing, P.R. China
2Biomedical Pioneering Innovation Center (BIOPIC), Peking University, Beijing, P.R. China
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: yunlongcao@pku.edu.cn ronghuajin@ccmu.edu.cn junyuxiao@pku.edu.cn sunneyxie@biopic.pku.edu.cn
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Supplementary material
  • Data/Code
  • Preview PDF
Loading

Abstract

Constantly emerging SARS-CoV-2 variants, such as Omicron BA.1, BA.1.1 and BA.2, pose a severe challenge to COVID-19 control1–10. Broad-spectrum antibody therapeutics and vaccines are needed for defending against future SARS-CoV-2 variants and sarbecovirus pandemics11–14; however, we have yet to gain a comprehensive understanding of the epitopes capable of inducing broad sarbecovirus neutralization. Here, we report the identification of 241 anti-RBD broad sarbecovirus neutralizing antibodies isolated from 44 SARS-CoV-2 vaccinated SARS convalescents. Neutralizing efficacy of these antibodies against D614G, SARS-CoV-1, Omicron variants (BA.1, BA.1.1, BA.2), RATG13 and Pangolin-GD is tested, and their binding capability to 21 sarbecovirus RBDs is measured. High-throughput yeast-display mutational screening was further applied to determine each antibody’s RBD escaping mutation profile, and unsupervised epitope clustering based on escaping mutation hotspots was performed7,15–18. A total of 6 clusters of broad sarbecovirus neutralizing antibodies with diverse breadth and epitopes were identified, namely Group E1 (S30919, BD55-3152 site), E3 (S2H9720 site), F1 (CR302221, S30422 site), F2 (DH104723, BD55-3500 site), F3 (ADG-224, BD55-3372 site) and B’ (S2K14625 site). Members of E1, F2 and F3 demonstrate the highest neutralization potency; yet, Omicron, especially BA.2, has evolved multiple mutations (G339D, N440K, T376A, D405N, R408S) to escape antibodies of these groups. Nevertheless, broad sarbecovirus neutralizing antibodies that survived Omicron would serve as favorable therapeutic candidates. Furthermore, structural analyses of selected drug candidates propose two non-competing antibody pairing strategies, E1-F2 and E1-F3, as broad-spectrum antibody cocktails. Together, our work provides a comprehensive epitope map of broad sarbecovirus neutralizing antibodies and offers critical instructions for designing broad-spectrum vaccines.

Competing Interest Statement

X.S.X. and Y.C. are listed as inventors on the provisional patent applications of BD series antibodies. X.S.X. and Y.C. are founders of Singlomics Biopharmaceuticals. The remaining authors declare no competing interests.

Footnotes

  • https://github.com/jianfcpku/SARS-CoV-2-RBD-DMS-broad

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
Back to top
PreviousNext
Posted February 07, 2022.
Download PDF

Supplementary Material

Data/Code
Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Comprehensive Epitope Mapping of Broad Sarbecovirus Neutralizing Antibodies
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Comprehensive Epitope Mapping of Broad Sarbecovirus Neutralizing Antibodies
Yunlong Cao, Ayijiang Yisimayi, Fanchong Jian, Tianhe Xiao, Weiliang Song, Jing Wang, Shuo Du, Zhiying Zhang, Pulan Liu, Xiaohua Hao, Qianqian Li, Peng Wang, Ran An, Yao Wang, Jing Wang, Haiyan Sun, Lijuan Zhao, Wen Zhang, Dong Zhao, Jiang Zheng, Lingling Yu, Can Li, Na Zhang, Rui Wang, Xiao Niu, Sijie Yang, Xuetao Song, Linlin Zheng, Zhiqiang Li, Qingqing Gu, Fei Shao, Weijin Huang, Youchun Wang, Ronghua Jin, Junyu Xiao, Xiaoliang Sunney Xie
bioRxiv 2022.02.07.479349; doi: https://doi.org/10.1101/2022.02.07.479349
Digg logo Reddit logo Twitter logo Facebook logo Google logo LinkedIn logo Mendeley logo
Citation Tools
Comprehensive Epitope Mapping of Broad Sarbecovirus Neutralizing Antibodies
Yunlong Cao, Ayijiang Yisimayi, Fanchong Jian, Tianhe Xiao, Weiliang Song, Jing Wang, Shuo Du, Zhiying Zhang, Pulan Liu, Xiaohua Hao, Qianqian Li, Peng Wang, Ran An, Yao Wang, Jing Wang, Haiyan Sun, Lijuan Zhao, Wen Zhang, Dong Zhao, Jiang Zheng, Lingling Yu, Can Li, Na Zhang, Rui Wang, Xiao Niu, Sijie Yang, Xuetao Song, Linlin Zheng, Zhiqiang Li, Qingqing Gu, Fei Shao, Weijin Huang, Youchun Wang, Ronghua Jin, Junyu Xiao, Xiaoliang Sunney Xie
bioRxiv 2022.02.07.479349; doi: https://doi.org/10.1101/2022.02.07.479349

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Immunology
Subject Areas
All Articles
  • Animal Behavior and Cognition (3603)
  • Biochemistry (7570)
  • Bioengineering (5526)
  • Bioinformatics (20798)
  • Biophysics (10329)
  • Cancer Biology (7985)
  • Cell Biology (11640)
  • Clinical Trials (138)
  • Developmental Biology (6605)
  • Ecology (10205)
  • Epidemiology (2065)
  • Evolutionary Biology (13620)
  • Genetics (9541)
  • Genomics (12847)
  • Immunology (7921)
  • Microbiology (19542)
  • Molecular Biology (7660)
  • Neuroscience (42109)
  • Paleontology (308)
  • Pathology (1258)
  • Pharmacology and Toxicology (2202)
  • Physiology (3267)
  • Plant Biology (7042)
  • Scientific Communication and Education (1294)
  • Synthetic Biology (1951)
  • Systems Biology (5426)
  • Zoology (1117)