Cargando…

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 are a major contributor to neutralizing antibody responses elicited by infection. Here, we describe a deep mutational scanning method to map how all amino-acid mutations in the RBD affect...

Descripción completa

Detalles Bibliográficos
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: Cell Press 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7676316/
https://www.ncbi.nlm.nih.gov/pubmed/33259788
http://dx.doi.org/10.1016/j.chom.2020.11.007
_version_ 1783611748427759616
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 are a major contributor to neutralizing antibody responses 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 surface often have distinct escape mutations. The complete escape maps predict which mutations are selected during viral growth in the presence of single antibodies. They further enable the design of escape-resistant antibody cocktails—including cocktails of antibodies that compete for binding to the same RBD surface 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.
format Online
Article
Text
id pubmed-7676316
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Cell Press
record_format MEDLINE/PubMed
spelling pubmed-76763162020-11-20 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. Cell Host Microbe Article Antibodies targeting the SARS-CoV-2 spike receptor-binding domain (RBD) are being developed as therapeutics and are a major contributor to neutralizing antibody responses 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 surface often have distinct escape mutations. The complete escape maps predict which mutations are selected during viral growth in the presence of single antibodies. They further enable the design of escape-resistant antibody cocktails—including cocktails of antibodies that compete for binding to the same RBD surface 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. Cell Press 2021-01-13 /pmc/articles/PMC7676316/ /pubmed/33259788 http://dx.doi.org/10.1016/j.chom.2020.11.007 Text en © 2020 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY 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/PMC7676316/
https://www.ncbi.nlm.nih.gov/pubmed/33259788
http://dx.doi.org/10.1016/j.chom.2020.11.007
work_keys_str_mv AT greaneyallisonj completemappingofmutationstothesarscov2spikereceptorbindingdomainthatescapeantibodyrecognition
AT starrtylern completemappingofmutationstothesarscov2spikereceptorbindingdomainthatescapeantibodyrecognition
AT gilchukpavlo completemappingofmutationstothesarscov2spikereceptorbindingdomainthatescapeantibodyrecognition
AT zostsethj completemappingofmutationstothesarscov2spikereceptorbindingdomainthatescapeantibodyrecognition
AT binshteinelad completemappingofmutationstothesarscov2spikereceptorbindingdomainthatescapeantibodyrecognition
AT loesandrean completemappingofmutationstothesarscov2spikereceptorbindingdomainthatescapeantibodyrecognition
AT hiltonsarahk completemappingofmutationstothesarscov2spikereceptorbindingdomainthatescapeantibodyrecognition
AT huddlestonjohn completemappingofmutationstothesarscov2spikereceptorbindingdomainthatescapeantibodyrecognition
AT eguiarachel completemappingofmutationstothesarscov2spikereceptorbindingdomainthatescapeantibodyrecognition
AT crawfordkatharinehd completemappingofmutationstothesarscov2spikereceptorbindingdomainthatescapeantibodyrecognition
AT dingensadams completemappingofmutationstothesarscov2spikereceptorbindingdomainthatescapeantibodyrecognition
AT nargirachels completemappingofmutationstothesarscov2spikereceptorbindingdomainthatescapeantibodyrecognition
AT suttonrachele completemappingofmutationstothesarscov2spikereceptorbindingdomainthatescapeantibodyrecognition
AT suryadevaranaveenchandra completemappingofmutationstothesarscov2spikereceptorbindingdomainthatescapeantibodyrecognition
AT rothlaufpaulw completemappingofmutationstothesarscov2spikereceptorbindingdomainthatescapeantibodyrecognition
AT liuzhuoming completemappingofmutationstothesarscov2spikereceptorbindingdomainthatescapeantibodyrecognition
AT whelanseanpj completemappingofmutationstothesarscov2spikereceptorbindingdomainthatescapeantibodyrecognition
AT carnahanroberth completemappingofmutationstothesarscov2spikereceptorbindingdomainthatescapeantibodyrecognition
AT crowejamese completemappingofmutationstothesarscov2spikereceptorbindingdomainthatescapeantibodyrecognition
AT bloomjessed completemappingofmutationstothesarscov2spikereceptorbindingdomainthatescapeantibodyrecognition