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.

doi:10.1016/j.chom.2020.11.012

D614G Spike Mutation Increases SARS CoV-2 Susceptibility to Neutralization

Journal Article · Mon Nov 30 23:00:00 EST 2020 · Cell Host & Microbe

DOI:https://doi.org/10.1016/j.chom.2020.11.012· OSTI ID:1734731

Weissman, Drew ^[1]; Alameh, Mohamad-Gabriel ^[1]; de Silva, Thushan ^[2]; Collini, Paul ^[2]; Hornsby, Hailey ^[2]; Brown, Rebecca ^[2]; LaBranche, Celia C. ^[3]; Edwards, Robert J. ^[3]; Sutherland, Laura ^[3]; Santra, Sampa ^[4]; Mansouri, Katayoun ^[3]; Gobeil, Sophie ^[3]; McDanal, Charlene ^[3]; Pardi, Norbert ^[1]; Hengartner, Nick ^[5]; Lin, Paulo J.C. ^[6]; Tam, Ying ^[6]; Shaw, Pamela A. ^[1]; Lewis, Mark G. ^[7]; Boesler, Carsten ^[8] more »

Univ. of Pennsylvania, Philadelphia, PA (United States)
Univ. of Sheffield (United Kingdom)
Duke Univ., Durham, NC (United States)
Harvard Medical School, Boston, MA (United States)
Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
Acuitas Theraputics, Vancouver, BC (Canada)
Bioqual Inc., Rockville, MD (United States)
BioNTech, Mainz (Germany)

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. Here, 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.

View Accepted Manuscript (DOE)

Research Organization:: Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)

Sponsoring Organization:: USDOE National Nuclear Security Administration (NNSA); USDOE Laboratory Directed Research and Development (LDRD) Program; National Institute of Allergy and Infectious Diseases (NIAID); National Institutes of Health (NIH); Wellcome Trust

Grant/Contract Number:: 89233218CNA000001

OSTI ID:: 1734731

Report Number(s):: LA-UR--20-25579

Journal Information:: Cell Host & Microbe, Journal Name: Cell Host & Microbe Journal Issue: 1 Vol. 29; ISSN 1931-3128

Publisher:: ElsevierCopyright Statement

Country of Publication:: United States

Language:: English

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electron micrograph
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nucleoside-modified
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D614G Spike Mutation Increases SARS CoV-2 Susceptibility to Neutralization

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