Cited by 332SARS-CoV-2 and COVID-19 Researchvaccines and immunoinformatics approachesAnimal Virus Infections Studies

D614G Spike Mutation Increases SARS CoV-2 Susceptibility to Neutralization

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Weissman, Drew, Alameh, Mohamad-Gabriel, de Silva, Thushan, Collini, Paul, Hornsby, Hailey, Brown, Rebecca, LaBranche, Celia C., Edwards, Robert J. +17 more·2021·Cell Host & Microbe

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Abstract

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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Authors
Weissman, D., Alameh, M.-G., de Silva, T., Collini, P., Hornsby, H., Brown, R., LaBranche, C. C., Edwards, R. J., Sutherland, L., Santra, S., Mansouri, K., Gobeil, S., McDanal, C., Pardi, N., Hengartner, N., Lin, P. J. C., Tam, Y., Shaw, P. A., Lewis, M. G., Boesler, C., Şahin, U., Acharya, P., Haynes, B. F., Korber, B., & Montefiori, D. C.
Affiliations
  • University of Pennsylvania (US)
  • Sheffield Teaching Hospitals NHS Foundation Trust (GB)
  • University of Sheffield (GB)
  • Duke University (US)
  • Beth Israel Deaconess Medical Center (US)
  • Acuitas Therapeutics (Canada) (CA)
  • Bioqual (US)
  • BioNTech (Germany) (DE)
  • Los Alamos National Laboratory (US)
Corresponding author
Weissman, Drew
Venue
Cell Host & Microbe
Publisher
Elsevier BV
Published
2021-01
Volume
29
Issue
1
Pages
23-31.e4
ISSN
1931-3128 (ISSN-L)
OpenAlex
W3108737416
Cited by
324
References
57
Citations by year
2026: 6 · 2025: 7 · 2024: 17 · 2023: 33 · 2022: 72 · 2021: 173 · 2020: 16
FWCI
9.59
Type
journal article
Language
en
Open access
Locations
  • Cell Host & Microbe (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • OSTI OAI (U.S. Department of Energy Office of Scientific and Technical Information) (submittedVersion)
Funders
  • National Institutes of Health (75N93019C00050, HHSN272201800004C, R01 - AI145687)
  • Wellcome Trust (110058/Z/15/Z)
  • National Institute of Allergy and Infectious Diseases (AI142596, AI124429, R01AI123738, 1R01AI146101)
  • University of Pennsylvania
  • National Institute for Health Research
  • Laboratory Directed Research and Development (20200706ER)
  • Bill and Melinda Gates Foundation (OPP1146996)
  • UK Research and Innovation
Topics
  • Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
  • Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Virus Infections Studies
Keywords
SARS-CoV-2, spike protein, D614G mutation, neutralizing antibodies, neutralization escape, receptor binding domain, monoclonal antibodies, convalescent sera, epitope exposure, vaccine efficacy, pseudovirus
MeSH terms
COVID-19, SARS-CoV-2, COVID-19 Vaccines, COVID-19 Serotherapy, Adolescent, Adult, Animals, Antibodies, Monoclonal, Binding Sites, Female, Humans, Immunization, Passive, Macaca mulatta, Male, Mice, Inbred BALB C, Middle Aged, Mutation, Neutralization Tests, Mice, Young Adult, HEK293 Cells, Spike Glycoprotein, Coronavirus

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