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Complete mapping of mutations to the SARS-CoV-2 spike receptor-binding domain that escape antibody recognition

Antibodies targeting the SARS-CoV-2 spike receptor-binding domain (RBD) are being developed as therapeutics and make a major contribution to the neutralizing antibody response elicited by infection. Here, we describe a deep mutational scanning method to map how all amino-acid mutations in the RBD af...

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Autores principales: Greaney, Allison J., Starr, Tyler N., Gilchuk, Pavlo, Zost, Seth J., Binshtein, Elad, Loes, Andrea N., Hilton, Sarah K., Huddleston, John, Eguia, Rachel, Crawford, Katharine H.D., Dingens, Adam S., Nargi, Rachel S., Sutton, Rachel E., Suryadevara, Naveenchandra, Rothlauf, Paul W., Liu, Zhuoming, Whelan, Sean P.J., Carnahan, Robert H., Crowe, James E., Bloom, Jesse D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7491521/
https://www.ncbi.nlm.nih.gov/pubmed/32935107
http://dx.doi.org/10.1101/2020.09.10.292078
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author Greaney, Allison J.
Starr, Tyler N.
Gilchuk, Pavlo
Zost, Seth J.
Binshtein, Elad
Loes, Andrea N.
Hilton, Sarah K.
Huddleston, John
Eguia, Rachel
Crawford, Katharine H.D.
Dingens, Adam S.
Nargi, Rachel S.
Sutton, Rachel E.
Suryadevara, Naveenchandra
Rothlauf, Paul W.
Liu, Zhuoming
Whelan, Sean P.J.
Carnahan, Robert H.
Crowe, James E.
Bloom, Jesse D.
author_facet Greaney, Allison J.
Starr, Tyler N.
Gilchuk, Pavlo
Zost, Seth J.
Binshtein, Elad
Loes, Andrea N.
Hilton, Sarah K.
Huddleston, John
Eguia, Rachel
Crawford, Katharine H.D.
Dingens, Adam S.
Nargi, Rachel S.
Sutton, Rachel E.
Suryadevara, Naveenchandra
Rothlauf, Paul W.
Liu, Zhuoming
Whelan, Sean P.J.
Carnahan, Robert H.
Crowe, James E.
Bloom, Jesse D.
author_sort Greaney, Allison J.
collection PubMed
description Antibodies targeting the SARS-CoV-2 spike receptor-binding domain (RBD) are being developed as therapeutics and make a major contribution to the neutralizing antibody response elicited by infection. Here, we describe a deep mutational scanning method to map how all amino-acid mutations in the RBD affect antibody binding, and apply this method to 10 human monoclonal antibodies. The escape mutations cluster on several surfaces of the RBD that broadly correspond to structurally defined antibody epitopes. However, even antibodies targeting the same RBD surface often have distinct escape mutations. The complete escape maps predict which mutations are selected during viral growth in the presence of single antibodies, and enable us to design escape-resistant antibody cocktails–including cocktails of antibodies that compete for binding to the same surface of the RBD but have different escape mutations. Therefore, complete escape-mutation maps enable rational design of antibody therapeutics and assessment of the antigenic consequences of viral evolution.
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spelling pubmed-74915212020-09-16 Complete mapping of mutations to the SARS-CoV-2 spike receptor-binding domain that escape antibody recognition Greaney, Allison J. Starr, Tyler N. Gilchuk, Pavlo Zost, Seth J. Binshtein, Elad Loes, Andrea N. Hilton, Sarah K. Huddleston, John Eguia, Rachel Crawford, Katharine H.D. Dingens, Adam S. Nargi, Rachel S. Sutton, Rachel E. Suryadevara, Naveenchandra Rothlauf, Paul W. Liu, Zhuoming Whelan, Sean P.J. Carnahan, Robert H. Crowe, James E. Bloom, Jesse D. bioRxiv Article Antibodies targeting the SARS-CoV-2 spike receptor-binding domain (RBD) are being developed as therapeutics and make a major contribution to the neutralizing antibody response elicited by infection. Here, we describe a deep mutational scanning method to map how all amino-acid mutations in the RBD affect antibody binding, and apply this method to 10 human monoclonal antibodies. The escape mutations cluster on several surfaces of the RBD that broadly correspond to structurally defined antibody epitopes. However, even antibodies targeting the same RBD surface often have distinct escape mutations. The complete escape maps predict which mutations are selected during viral growth in the presence of single antibodies, and enable us to design escape-resistant antibody cocktails–including cocktails of antibodies that compete for binding to the same surface of the RBD but have different escape mutations. Therefore, complete escape-mutation maps enable rational design of antibody therapeutics and assessment of the antigenic consequences of viral evolution. Cold Spring Harbor Laboratory 2020-09-28 /pmc/articles/PMC7491521/ /pubmed/32935107 http://dx.doi.org/10.1101/2020.09.10.292078 Text en http://creativecommons.org/licenses/by/4.0/It is made available under a CC-BY 4.0 International license (http://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Greaney, Allison J.
Starr, Tyler N.
Gilchuk, Pavlo
Zost, Seth J.
Binshtein, Elad
Loes, Andrea N.
Hilton, Sarah K.
Huddleston, John
Eguia, Rachel
Crawford, Katharine H.D.
Dingens, Adam S.
Nargi, Rachel S.
Sutton, Rachel E.
Suryadevara, Naveenchandra
Rothlauf, Paul W.
Liu, Zhuoming
Whelan, Sean P.J.
Carnahan, Robert H.
Crowe, James E.
Bloom, Jesse D.
Complete mapping of mutations to the SARS-CoV-2 spike receptor-binding domain that escape antibody recognition
title Complete mapping of mutations to the SARS-CoV-2 spike receptor-binding domain that escape antibody recognition
title_full Complete mapping of mutations to the SARS-CoV-2 spike receptor-binding domain that escape antibody recognition
title_fullStr Complete mapping of mutations to the SARS-CoV-2 spike receptor-binding domain that escape antibody recognition
title_full_unstemmed Complete mapping of mutations to the SARS-CoV-2 spike receptor-binding domain that escape antibody recognition
title_short Complete mapping of mutations to the SARS-CoV-2 spike receptor-binding domain that escape antibody recognition
title_sort complete mapping of mutations to the sars-cov-2 spike receptor-binding domain that escape antibody recognition
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7491521/
https://www.ncbi.nlm.nih.gov/pubmed/32935107
http://dx.doi.org/10.1101/2020.09.10.292078
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