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D614G Spike Mutation Increases SARS CoV-2 Susceptibility to Neutralization

Cell Host & Microbe, 2021-01, Vol.29 (1), p.23-31.e4 [Peer Reviewed Journal]

2020 ;Copyright © 2020. Published by Elsevier Inc. ;2020. Not withstanding the ProQuest Terms and Conditions, you may use this content in accordance with the associated terms available at https://www.elsevier.com/legal/elsevier-website-terms-and-conditions ;2020 Published by Elsevier Inc. 2020 ;ISSN: 1931-3128 ;EISSN: 1934-6069 ;DOI: 10.1016/j.chom.2020.11.012 ;PMID: 33306985

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Title:
D614G Spike Mutation Increases SARS CoV-2 Susceptibility to Neutralization
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.
Subjects: 60 APPLIED LIFE SCIENCES ; Adolescent ; Adult ; Animals ; Antibodies, Monoclonal - immunology ; Binding Sites ; COVID-19 ; COVID-19 - immunology ; COVID-19 - therapy ; COVID-19 Serotherapy ; COVID-19 Vaccines - immunology ; D614G ; electron micrograph ; Female ; HEK293 Cells ; Humans ; Immunization, Passive - methods ; LNP ; Macaca mulatta ; Male ; Mice ; Mice, Inbred BALB C ; Middle Aged ; mRNA ; Mutation ; neutralization ; Neutralization Tests ; nucleoside-modified ; SARS-CoV-2 ; SARS-CoV-2 - genetics ; SARS-CoV-2 - pathogenicity ; Short ; Spike ; Spike Glycoprotein, Coronavirus - chemistry ; Spike Glycoprotein, Coronavirus - genetics ; Spike Glycoprotein, Coronavirus - immunology ; vaccine ; Young Adult
Is Part Of: Cell Host & Microbe, 2021-01, Vol.29 (1), p.23-31.e4
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. [Display omitted] •Spike-based SARS-CoV-2 vaccines potently neutralize the globally dominant G614 variant•Vaccinated and immune sera neutralize G614 better than the original spike•The structure of the G614 spike demonstrates a more open position of the RBD Serum from SARS-CoV-2 spike-vaccinated mice, NHPs and humans, and convalescent patients, along with receptor-binding domain (RBD)-specific monoclonal antibodies neutralize the widespread G614-containing virus at greater levels than the original D614 version. Structural data demonstrate that the G614 spike is in a more open conformation with extended RBDs.
Publisher: United States: Elsevier Inc
Language: English
Identifier: ISSN: 1931-3128
EISSN: 1934-6069
DOI: 10.1016/j.chom.2020.11.012
PMID: 33306985
Source: Coronavirus Research Database

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D614G Spike Mutation Increases SARS CoV-2 Susceptibility to Neutralization

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