The antigenic anatomy of SARS-CoV-2 receptor binding domain
Antibodies are crucial to immune protection against SARS-CoV-2, with some in emergency use as therapeutics. Here, we identify 377 human monoclonal antibodies (mAbs) recognizing the virus spike and focus mainly on 80 that bind the receptor binding domain (RBD). We devise a competition data-driven met...
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th-mahidol.762092022-08-04T15:10:10Z The antigenic anatomy of SARS-CoV-2 receptor binding domain Wanwisa Dejnirattisai Daming Zhou Helen M. Ginn Helen M.E. Duyvesteyn Piyada Supasa James Brett Case Yuguang Zhao Thomas S. Walter Alexander J. Mentzer Chang Liu Beibei Wang Guido C. Paesen Jose Slon-Campos César López-Camacho Natasha M. Kafai Adam L. Bailey Rita E. Chen Baoling Ying Craig Thompson Jai Bolton Alex Fyfe Sunetra Gupta Tiong Kit Tan Javier Gilbert-Jaramillo William James Michael Knight Miles W. Carroll Donal Skelly Christina Dold Yanchun Peng Robert Levin Tao Dong Andrew J. Pollard Julian C. Knight Paul Klenerman Nigel Temperton David R. Hall Mark A. Williams Neil G. Paterson Felicity K.R. Bertram C. Alistair Siebert Daniel K. Clare Andrew Howe Julika Radecke Yun Song Alain R. Townsend Kuan Ying A. Huang Elizabeth E. Fry Juthathip Mongkolsapaya Michael S. Diamond Jingshan Ren David I. Stuart Gavin R. Screaton NIHR Oxford Biomedical Research Centre Oxford University Hospitals NHS Foundation Trust Public Health England Diamond Light Source Chang Gung University College of Medicine Chang Gung Memorial Hospital Worthing Hospital University of Oxford Washington University School of Medicine in St. Louis Sir William Dunn School of Pathology Faculty of Medicine Siriraj Hospital, Mahidol University University of Kent Nuffield Department of Medicine University of Oxford Medical Sciences Division Instruct-ERIC Biochemistry, Genetics and Molecular Biology Antibodies are crucial to immune protection against SARS-CoV-2, with some in emergency use as therapeutics. Here, we identify 377 human monoclonal antibodies (mAbs) recognizing the virus spike and focus mainly on 80 that bind the receptor binding domain (RBD). We devise a competition data-driven method to map RBD binding sites. We find that although antibody binding sites are widely dispersed, neutralizing antibody binding is focused, with nearly all highly inhibitory mAbs (IC50 < 0.1 μg/mL) blocking receptor interaction, except for one that binds a unique epitope in the N-terminal domain. Many of these neutralizing mAbs use public V-genes and are close to germline. We dissect the structural basis of recognition for this large panel of antibodies through X-ray crystallography and cryoelectron microscopy of 19 Fab-antigen structures. We find novel binding modes for some potently inhibitory antibodies and demonstrate that strongly neutralizing mAbs protect, prophylactically or therapeutically, in animal models. 2022-08-04T08:10:10Z 2022-08-04T08:10:10Z 2021-04-15 Article Cell. Vol.184, No.8 (2021), 2183-2200.e22 10.1016/j.cell.2021.02.032 10974172 00928674 2-s2.0-85102643098 https://repository.li.mahidol.ac.th/handle/123456789/76209 Mahidol University SCOPUS https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85102643098&origin=inward |
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Biochemistry, Genetics and Molecular Biology Wanwisa Dejnirattisai Daming Zhou Helen M. Ginn Helen M.E. Duyvesteyn Piyada Supasa James Brett Case Yuguang Zhao Thomas S. Walter Alexander J. Mentzer Chang Liu Beibei Wang Guido C. Paesen Jose Slon-Campos César López-Camacho Natasha M. Kafai Adam L. Bailey Rita E. Chen Baoling Ying Craig Thompson Jai Bolton Alex Fyfe Sunetra Gupta Tiong Kit Tan Javier Gilbert-Jaramillo William James Michael Knight Miles W. Carroll Donal Skelly Christina Dold Yanchun Peng Robert Levin Tao Dong Andrew J. Pollard Julian C. Knight Paul Klenerman Nigel Temperton David R. Hall Mark A. Williams Neil G. Paterson Felicity K.R. Bertram C. Alistair Siebert Daniel K. Clare Andrew Howe Julika Radecke Yun Song Alain R. Townsend Kuan Ying A. Huang Elizabeth E. Fry Juthathip Mongkolsapaya Michael S. Diamond Jingshan Ren David I. Stuart Gavin R. Screaton The antigenic anatomy of SARS-CoV-2 receptor binding domain |
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Antibodies are crucial to immune protection against SARS-CoV-2, with some in emergency use as therapeutics. Here, we identify 377 human monoclonal antibodies (mAbs) recognizing the virus spike and focus mainly on 80 that bind the receptor binding domain (RBD). We devise a competition data-driven method to map RBD binding sites. We find that although antibody binding sites are widely dispersed, neutralizing antibody binding is focused, with nearly all highly inhibitory mAbs (IC50 < 0.1 μg/mL) blocking receptor interaction, except for one that binds a unique epitope in the N-terminal domain. Many of these neutralizing mAbs use public V-genes and are close to germline. We dissect the structural basis of recognition for this large panel of antibodies through X-ray crystallography and cryoelectron microscopy of 19 Fab-antigen structures. We find novel binding modes for some potently inhibitory antibodies and demonstrate that strongly neutralizing mAbs protect, prophylactically or therapeutically, in animal models. |
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NIHR Oxford Biomedical Research Centre |
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NIHR Oxford Biomedical Research Centre Wanwisa Dejnirattisai Daming Zhou Helen M. Ginn Helen M.E. Duyvesteyn Piyada Supasa James Brett Case Yuguang Zhao Thomas S. Walter Alexander J. Mentzer Chang Liu Beibei Wang Guido C. Paesen Jose Slon-Campos César López-Camacho Natasha M. Kafai Adam L. Bailey Rita E. Chen Baoling Ying Craig Thompson Jai Bolton Alex Fyfe Sunetra Gupta Tiong Kit Tan Javier Gilbert-Jaramillo William James Michael Knight Miles W. Carroll Donal Skelly Christina Dold Yanchun Peng Robert Levin Tao Dong Andrew J. Pollard Julian C. Knight Paul Klenerman Nigel Temperton David R. Hall Mark A. Williams Neil G. Paterson Felicity K.R. Bertram C. Alistair Siebert Daniel K. Clare Andrew Howe Julika Radecke Yun Song Alain R. Townsend Kuan Ying A. Huang Elizabeth E. Fry Juthathip Mongkolsapaya Michael S. Diamond Jingshan Ren David I. Stuart Gavin R. Screaton |
format |
Article |
author |
Wanwisa Dejnirattisai Daming Zhou Helen M. Ginn Helen M.E. Duyvesteyn Piyada Supasa James Brett Case Yuguang Zhao Thomas S. Walter Alexander J. Mentzer Chang Liu Beibei Wang Guido C. Paesen Jose Slon-Campos César López-Camacho Natasha M. Kafai Adam L. Bailey Rita E. Chen Baoling Ying Craig Thompson Jai Bolton Alex Fyfe Sunetra Gupta Tiong Kit Tan Javier Gilbert-Jaramillo William James Michael Knight Miles W. Carroll Donal Skelly Christina Dold Yanchun Peng Robert Levin Tao Dong Andrew J. Pollard Julian C. Knight Paul Klenerman Nigel Temperton David R. Hall Mark A. Williams Neil G. Paterson Felicity K.R. Bertram C. Alistair Siebert Daniel K. Clare Andrew Howe Julika Radecke Yun Song Alain R. Townsend Kuan Ying A. Huang Elizabeth E. Fry Juthathip Mongkolsapaya Michael S. Diamond Jingshan Ren David I. Stuart Gavin R. Screaton |
author_sort |
Wanwisa Dejnirattisai |
title |
The antigenic anatomy of SARS-CoV-2 receptor binding domain |
title_short |
The antigenic anatomy of SARS-CoV-2 receptor binding domain |
title_full |
The antigenic anatomy of SARS-CoV-2 receptor binding domain |
title_fullStr |
The antigenic anatomy of SARS-CoV-2 receptor binding domain |
title_full_unstemmed |
The antigenic anatomy of SARS-CoV-2 receptor binding domain |
title_sort |
antigenic anatomy of sars-cov-2 receptor binding domain |
publishDate |
2022 |
url |
https://repository.li.mahidol.ac.th/handle/123456789/76209 |
_version_ |
1763492412596944896 |