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Antibody cocktail to SARS-CoV-2 spike protein prevents rapid mutational escape seen with individual antibodies

Antibodies targeting the spike protein of SARS-CoV-2 present a promising approach to combat the COVID19 pandemic; however, concerns remain that mutations can yield antibody resistance. We investigate the development of resistance against four antibodies to the spike protein that potently neutralize...

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Autores principales: Baum, Alina, Fulton, Benjamin O., Wloga, Elzbieta, Copin, Richard, Pascal, Kristen E., Russo, Vincenzo, Giordano, Stephanie, Lanza, Kathryn, Negron, Nicole, Ni, Min, Wei, Yi, Atwal, Gurinder S., Murphy, Andrew J., Stahl, Neil, Yancopoulos, George D., Kyratsous, Christos A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7299283/
https://www.ncbi.nlm.nih.gov/pubmed/32540904
http://dx.doi.org/10.1126/science.abd0831
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author Baum, Alina
Fulton, Benjamin O.
Wloga, Elzbieta
Copin, Richard
Pascal, Kristen E.
Russo, Vincenzo
Giordano, Stephanie
Lanza, Kathryn
Negron, Nicole
Ni, Min
Wei, Yi
Atwal, Gurinder S.
Murphy, Andrew J.
Stahl, Neil
Yancopoulos, George D.
Kyratsous, Christos A.
author_facet Baum, Alina
Fulton, Benjamin O.
Wloga, Elzbieta
Copin, Richard
Pascal, Kristen E.
Russo, Vincenzo
Giordano, Stephanie
Lanza, Kathryn
Negron, Nicole
Ni, Min
Wei, Yi
Atwal, Gurinder S.
Murphy, Andrew J.
Stahl, Neil
Yancopoulos, George D.
Kyratsous, Christos A.
author_sort Baum, Alina
collection PubMed
description Antibodies targeting the spike protein of SARS-CoV-2 present a promising approach to combat the COVID19 pandemic; however, concerns remain that mutations can yield antibody resistance. We investigate the development of resistance against four antibodies to the spike protein that potently neutralize SARS-CoV-2, individually as well as when combined into cocktails. These antibodies remain effective against spike variants that have arisen in the human population. However, novel spike mutants rapidly appeared following in vitro passaging in the presence of individual antibodies, resulting in loss of neutralization; such escape also occurred with combinations of antibodies binding diverse but overlapping regions of the spike protein. Importantly, escape mutants were not generated following treatment with a non-competing antibody cocktail.
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spelling pubmed-72992832020-06-29 Antibody cocktail to SARS-CoV-2 spike protein prevents rapid mutational escape seen with individual antibodies Baum, Alina Fulton, Benjamin O. Wloga, Elzbieta Copin, Richard Pascal, Kristen E. Russo, Vincenzo Giordano, Stephanie Lanza, Kathryn Negron, Nicole Ni, Min Wei, Yi Atwal, Gurinder S. Murphy, Andrew J. Stahl, Neil Yancopoulos, George D. Kyratsous, Christos A. Science Reports Antibodies targeting the spike protein of SARS-CoV-2 present a promising approach to combat the COVID19 pandemic; however, concerns remain that mutations can yield antibody resistance. We investigate the development of resistance against four antibodies to the spike protein that potently neutralize SARS-CoV-2, individually as well as when combined into cocktails. These antibodies remain effective against spike variants that have arisen in the human population. However, novel spike mutants rapidly appeared following in vitro passaging in the presence of individual antibodies, resulting in loss of neutralization; such escape also occurred with combinations of antibodies binding diverse but overlapping regions of the spike protein. Importantly, escape mutants were not generated following treatment with a non-competing antibody cocktail. American Association for the Advancement of Science 2020-06-15 /pmc/articles/PMC7299283/ /pubmed/32540904 http://dx.doi.org/10.1126/science.abd0831 Text en Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY). http://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/) , which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited.
spellingShingle Reports
Baum, Alina
Fulton, Benjamin O.
Wloga, Elzbieta
Copin, Richard
Pascal, Kristen E.
Russo, Vincenzo
Giordano, Stephanie
Lanza, Kathryn
Negron, Nicole
Ni, Min
Wei, Yi
Atwal, Gurinder S.
Murphy, Andrew J.
Stahl, Neil
Yancopoulos, George D.
Kyratsous, Christos A.
Antibody cocktail to SARS-CoV-2 spike protein prevents rapid mutational escape seen with individual antibodies
title Antibody cocktail to SARS-CoV-2 spike protein prevents rapid mutational escape seen with individual antibodies
title_full Antibody cocktail to SARS-CoV-2 spike protein prevents rapid mutational escape seen with individual antibodies
title_fullStr Antibody cocktail to SARS-CoV-2 spike protein prevents rapid mutational escape seen with individual antibodies
title_full_unstemmed Antibody cocktail to SARS-CoV-2 spike protein prevents rapid mutational escape seen with individual antibodies
title_short Antibody cocktail to SARS-CoV-2 spike protein prevents rapid mutational escape seen with individual antibodies
title_sort antibody cocktail to sars-cov-2 spike protein prevents rapid mutational escape seen with individual antibodies
topic Reports
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7299283/
https://www.ncbi.nlm.nih.gov/pubmed/32540904
http://dx.doi.org/10.1126/science.abd0831
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