Scholars@Duke publication: D614G Spike Mutation Increases SARS CoV-2 Susceptibility to Neutralization.

D614G Spike Mutation Increases SARS CoV-2 Susceptibility to Neutralization.

Publication , Journal Article

Weissman, D; Alameh, M-G; de Silva, T; Collini, P; Hornsby, H; Brown, R; LaBranche, CC; Edwards, RJ; Sutherland, L; Santra, S; Mansouri, K ...

Published in: Cell Host Microbe

January 13, 2021

Published version (DOI) Link to item

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.

Duke Scholars

Author Priyamvada Acharya Surgery, Surgical Sciences

Author David Charles Montefiori Surgery, Surgical Sciences

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Published In

Cell Host Microbe

DOI

10.1016/j.chom.2020.11.012

EISSN

1934-6069

Publication Date

January 13, 2021

Volume

Issue

Start / End Page

23 / 31.e4

Location

United States

Related Subject Headings

Young Adult
Spike Glycoprotein, Coronavirus
SARS-CoV-2
Neutralization Tests
Mutation
Middle Aged
Mice, Inbred BALB C
Mice
Male
Macaca mulatta

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Weissman, D., Alameh, M.-G., de Silva, T., Collini, P., Hornsby, H., Brown, R., … Montefiori, D. C. (2021). D614G Spike Mutation Increases SARS CoV-2 Susceptibility to Neutralization. Cell Host Microbe, 29(1), 23-31.e4. https://doi.org/10.1016/j.chom.2020.11.012

Weissman, Drew, Mohamad-Gabriel Alameh, Thushan de Silva, Paul Collini, Hailey Hornsby, Rebecca Brown, Celia C. LaBranche, et al. “D614G Spike Mutation Increases SARS CoV-2 Susceptibility to Neutralization.” Cell Host Microbe 29, no. 1 (January 13, 2021): 23-31.e4. https://doi.org/10.1016/j.chom.2020.11.012.

Weissman D, Alameh M-G, de Silva T, Collini P, Hornsby H, Brown R, et al. D614G Spike Mutation Increases SARS CoV-2 Susceptibility to Neutralization. Cell Host Microbe. 2021 Jan 13;29(1):23-31.e4.

Weissman, Drew, et al. “D614G Spike Mutation Increases SARS CoV-2 Susceptibility to Neutralization.” Cell Host Microbe, vol. 29, no. 1, Jan. 2021, pp. 23-31.e4. Pubmed, doi:10.1016/j.chom.2020.11.012.

Weissman D, Alameh M-G, de Silva T, Collini P, Hornsby H, Brown R, LaBranche CC, Edwards RJ, Sutherland L, Santra S, Mansouri K, Gobeil S, McDanal C, Pardi N, Hengartner N, Lin PJC, Tam Y, Shaw PA, Lewis MG, Boesler C, Şahin U, Acharya P, Haynes BF, Korber B, Montefiori DC. D614G Spike Mutation Increases SARS CoV-2 Susceptibility to Neutralization. Cell Host Microbe. 2021 Jan 13;29(1):23-31.e4.

Published In

Cell Host Microbe

DOI

10.1016/j.chom.2020.11.012

EISSN

1934-6069

Publication Date

January 13, 2021

Volume

Issue

Start / End Page

23 / 31.e4

Location

United States

Related Subject Headings

Young Adult
Spike Glycoprotein, Coronavirus
SARS-CoV-2
Neutralization Tests
Mutation
Middle Aged
Mice, Inbred BALB C
Mice
Male
Macaca mulatta