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D614G Spike Mutation Increases SARS CoV-2 Susceptibility to Neutralization
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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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“Similar to previous studies from our group (15) and others (18), pseudovirus neutralization titers to D614G were threefold higher than to WA1 (Fig. 2G).”
From Durability of mRNA-1273 vaccine–induced antibodies against SARS-CoV-2 variants (2021) · cites this paper as [18]
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Metadata
- 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
- ORCID
- Weissman, Drew
- Alameh, Mohamad-Gabriel
- Collini, Paul
- Hornsby, Hailey
- Brown, Rebecca
- LaBranche, Celia C.
- Edwards, Robert J.
- Sutherland, Laura
- Santra, Sampa
- Mansouri, Katayoun
- Gobeil, Sophie
- McDanal, Charlene
- Pardi, Norbert
- 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.
- Venue
- Cell Host & Microbe
- Publisher
- Elsevier BV
- Published
- 2021-01
- Volume
- 29
- Issue
- 1
- Pages
- 23-31.e4
- ISSN
- 1931-3128 (ISSN-L)
- PMC
- PMC7707640
- OpenAlex
- W3108737416
- Cited by
- 324
- References
- 57
- Citations by year
- 2026: 6 · 2025: 7 · 2024: 17 · 2023: 33 · 2022: 72 · 2021: 173
- FWCI
- 9.59
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- 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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