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D614G Spike Mutation Increases SARS CoV-2 Susceptibility to Neutralization

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein acquired a D614G mutation early in the pandemic that confers greater infectivity and is now the globally dominant form. To determine whether D614G might also mediate neutralization escape that could compromise vaccine eff...

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Autores principales: Weissman, Drew, Alameh, Mohamad-Gabriel, de Silva, Thushan, Collini, Paul, Hornsby, Hailey, Brown, Rebecca, LaBranche, Celia C., Edwards, Robert J., Sutherland, Laura, Santra, Sampa, Mansouri, Katayoun, Gobeil, Sophie, McDanal, Charlene, Pardi, Norbert, Hengartner, Nick, Lin, Paulo J.C., Tam, Ying, Shaw, Pamela A., Lewis, Mark G., Boesler, Carsten, Şahin, Uğur, Acharya, Priyamvada, Haynes, Barton F., Korber, Bette, Montefiori, David C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Published by Elsevier Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7707640/
https://www.ncbi.nlm.nih.gov/pubmed/33306985
http://dx.doi.org/10.1016/j.chom.2020.11.012
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author Weissman, Drew
Alameh, Mohamad-Gabriel
de Silva, Thushan
Collini, Paul
Hornsby, Hailey
Brown, Rebecca
LaBranche, Celia C.
Edwards, Robert J.
Sutherland, Laura
Santra, Sampa
Mansouri, Katayoun
Gobeil, Sophie
McDanal, Charlene
Pardi, Norbert
Hengartner, Nick
Lin, Paulo J.C.
Tam, Ying
Shaw, Pamela A.
Lewis, Mark G.
Boesler, Carsten
Şahin, Uğur
Acharya, Priyamvada
Haynes, Barton F.
Korber, Bette
Montefiori, David C.
author_facet Weissman, Drew
Alameh, Mohamad-Gabriel
de Silva, Thushan
Collini, Paul
Hornsby, Hailey
Brown, Rebecca
LaBranche, Celia C.
Edwards, Robert J.
Sutherland, Laura
Santra, Sampa
Mansouri, Katayoun
Gobeil, Sophie
McDanal, Charlene
Pardi, Norbert
Hengartner, Nick
Lin, Paulo J.C.
Tam, Ying
Shaw, Pamela A.
Lewis, Mark G.
Boesler, Carsten
Şahin, Uğur
Acharya, Priyamvada
Haynes, Barton F.
Korber, Bette
Montefiori, David C.
author_sort Weissman, Drew
collection PubMed
description The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein acquired a D614G mutation early in the pandemic that confers greater infectivity and is now the globally dominant form. To determine whether D614G might also mediate neutralization escape that could compromise vaccine efficacy, sera from spike-immunized mice, nonhuman primates, and humans were evaluated for neutralization of pseudoviruses bearing either D614 or G614 spike. In all cases, the G614 pseudovirus was moderately more susceptible to neutralization. The G614 pseudovirus also was more susceptible to neutralization by receptor-binding domain (RBD) monoclonal antibodies and convalescent sera from people infected with either form of the virus. Negative stain electron microscopy revealed a higher percentage of the 1-RBD “up” conformation in the G614 spike, suggesting increased epitope exposure as a mechanism of enhanced vulnerability to neutralization. Based on these findings, the D614G mutation is not expected to be an obstacle for current vaccine development.
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spelling pubmed-77076402020-12-02 D614G Spike Mutation Increases SARS CoV-2 Susceptibility to Neutralization Weissman, Drew Alameh, Mohamad-Gabriel de Silva, Thushan Collini, Paul Hornsby, Hailey Brown, Rebecca LaBranche, Celia C. Edwards, Robert J. Sutherland, Laura Santra, Sampa Mansouri, Katayoun Gobeil, Sophie McDanal, Charlene Pardi, Norbert Hengartner, Nick Lin, Paulo J.C. Tam, Ying Shaw, Pamela A. Lewis, Mark G. Boesler, Carsten Şahin, Uğur Acharya, Priyamvada Haynes, Barton F. Korber, Bette Montefiori, David C. Cell Host Microbe Short Article The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein acquired a D614G mutation early in the pandemic that confers greater infectivity and is now the globally dominant form. To determine whether D614G might also mediate neutralization escape that could compromise vaccine efficacy, sera from spike-immunized mice, nonhuman primates, and humans were evaluated for neutralization of pseudoviruses bearing either D614 or G614 spike. In all cases, the G614 pseudovirus was moderately more susceptible to neutralization. The G614 pseudovirus also was more susceptible to neutralization by receptor-binding domain (RBD) monoclonal antibodies and convalescent sera from people infected with either form of the virus. Negative stain electron microscopy revealed a higher percentage of the 1-RBD “up” conformation in the G614 spike, suggesting increased epitope exposure as a mechanism of enhanced vulnerability to neutralization. Based on these findings, the D614G mutation is not expected to be an obstacle for current vaccine development. Published by Elsevier Inc. 2021-01-13 2020-12-01 /pmc/articles/PMC7707640/ /pubmed/33306985 http://dx.doi.org/10.1016/j.chom.2020.11.012 Text en © 2020 Published by Elsevier Inc. Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
spellingShingle Short Article
Weissman, Drew
Alameh, Mohamad-Gabriel
de Silva, Thushan
Collini, Paul
Hornsby, Hailey
Brown, Rebecca
LaBranche, Celia C.
Edwards, Robert J.
Sutherland, Laura
Santra, Sampa
Mansouri, Katayoun
Gobeil, Sophie
McDanal, Charlene
Pardi, Norbert
Hengartner, Nick
Lin, Paulo J.C.
Tam, Ying
Shaw, Pamela A.
Lewis, Mark G.
Boesler, Carsten
Şahin, Uğur
Acharya, Priyamvada
Haynes, Barton F.
Korber, Bette
Montefiori, David C.
D614G Spike Mutation Increases SARS CoV-2 Susceptibility to Neutralization
title D614G Spike Mutation Increases SARS CoV-2 Susceptibility to Neutralization
title_full D614G Spike Mutation Increases SARS CoV-2 Susceptibility to Neutralization
title_fullStr D614G Spike Mutation Increases SARS CoV-2 Susceptibility to Neutralization
title_full_unstemmed D614G Spike Mutation Increases SARS CoV-2 Susceptibility to Neutralization
title_short D614G Spike Mutation Increases SARS CoV-2 Susceptibility to Neutralization
title_sort d614g spike mutation increases sars cov-2 susceptibility to neutralization
topic Short Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7707640/
https://www.ncbi.nlm.nih.gov/pubmed/33306985
http://dx.doi.org/10.1016/j.chom.2020.11.012
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