Structural and functional ramifications of antigenic drift in recent SARS-CoV-2 variants
Open accessAbstract
The protective efficacy of neutralizing antibodies (nAbs) elicited during natural infection with SARS-CoV-2 and by vaccination based on its spike protein has been compromised with emergence of the recent SARS-CoV-2 variants. Residues E484 and K417 in the receptor-binding site (RBS) are both mutated in lineages first described in South Africa (B.1.351) and Brazil (B.1.1.28.1). The nAbs isolated from SARS-CoV-2 patients are preferentially encoded by certain heavy-chain germline genes and the two most frequently elicited antibody families (IGHV3-53/3-66 and IGHV1-2) can each bind the RBS in two different binding modes. However, their binding and neutralization are abrogated by either the E484K or K417N mutation, whereas nAbs to the cross-reactive CR3022 and S309 sites are largely unaffected. This structural and functional analysis illustrates why mutations at E484 and K417 adversely affect major classes of nAbs to SARS-CoV-2 with consequences for next-generation COVID-19 vaccines.
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The B.1.351 and P.1 SARS-CoV-2 variants carry a glutamate-to-lysine mutation at position 484 (E484K) in the spike protein receptor-binding domain, which promotes immune evasion.
“The B.1.351 and P.1 variants have a glutamate (E) to lysine (K) mutation at position 484 (E484K) in the receptor-binding domain of the spike protein, which promotes immune evasion207.”
From mRNA vaccines for infectious diseases: principles, delivery and clinical translation (2021) · cites this paper as [207]
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- Authors
- Yuan, M., Huang, D., Lee, C.-C. D., Wu, N. C., Jackson, A. M., Zhu, X., Liu, H., Peng, L., van Gils, M. J., Sanders, R. W., Burton, D. R., Reincke, S. M., Prüss, H., Kreye, J., Nemazee, D., Ward, A. B., & Wilson, I. A.
- Affiliations
- Scripps Research Institute (US)
- University of Illinois Urbana-Champaign (US)
- Cornell University (US)
- German Center for Neurodegenerative Diseases (DE)
- Corresponding author
- Wilson, Ian A.
- ORCID
- Venue
- Science
- Publisher
- openRxiv
- Published
- 2021-02-17
- Volume
- 373
- Issue
- 6556
- Pages
- 818-823
- ISSN
- 0036-8075 (ISSN-L)
- PMC
- PMC7899451
- OpenAlex
- W3160471157
- Cited by
- 364
- References
- 112
- Citations by year
- 2026: 11 · 2025: 27 · 2024: 35 · 2023: 60 · 2022: 138 · 2021: 92 · 2020: 1
- FWCI
- 25.73
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by
- Locations
- Science (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (submittedVersion, cc-by)
- PubMed Central (submittedVersion, cc-by-nc)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- OSTI OAI (U.S. Department of Energy Office of Scientific and Technical Information) (submittedVersion)
- DZNE Pub (submittedVersion)
- Funders
- U.S. Department of Energy (DE‐ AC02‐06CH11357, COVID-19, Contract No. DE-AC02-06CH11357., AC02‐06CH11357, 06CH11357, No. DE-AC02-06CH11357, DE-AC02-)
- Bill and Melinda Gates Foundation (INV-004923, OPP1170236, OPP1170236 and INV-004923)
- Helmholtz-Gemeinschaft (HIL-A03 and SO-097)
- Deutsche Forschungsgemeinschaft (PR1274/5–1, and PR 1274/5-1, DE-AC02-06CH11357, PR1274/3–1, PR 1274/3-1, and PR 1274/5-1)
- Bundesministerium für Bildung und Forschung (01GM1908D)
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek
- National Institutes of Health (COVID-19, DE-AC02–06CH11357, AI110657)
- Office of Science (Contract No. DE-AC02-06CH11357, AC02‐06CH11357, DE-AC02, No. DE-AC02-06CH11357., 06CH11357, DE-AC02-06CH11357)
- National Institute of Allergy and Infectious Diseases (R01AI142945, R01AI132317, P01AI110657, R00AI139445)
- Argonne National Laboratory (DE- AC02-06-CH11357, DE-AC02, AC02–06CH11357, No. DE-AC02-06CH11357, 06CH11357, Contract No. DE-AC02-06CH11357.)
- 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, antigenic drift, Beta variant, P.1, spike protein mutations, K417N, E484K, receptor binding sites, ACE2 binding, neutralizing antibodies, CR3022, vaccine design, antibody therapy
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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