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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 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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Antibody feedback regulation of memory B cell development in SARS-CoV-2 mRNA vaccinationPreprint
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Convergence of immune escape strategies highlights plasticity of SARS-CoV-2 spike
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Therapeutic antibodies and alternative formats against SARS-CoV-2
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Self-citationIFN-λ uniquely promotes CD8 T cell immunity against SARS-CoV-2 relative to type I IFN
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Self-citationSARS-CoV-2 variants resist antibody neutralization and broaden host ACE2 usagePreprint
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Self-citationPerformance Evaluation of Lateral Flow Assays for Coronavirus Disease-19 Serology
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SARS‐CoV‐2 evolves to reduce but not abolish neutralizing action
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When Do We Need Massive Computations to Perform Detailed COVID‐19 Simulations?
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Omicron BA.2 specifically evades broad sarbecovirus neutralizing antibodiesPreprint
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Antibody Cocktail Exhibits Broad Neutralization Activity Against SARS-CoV-2 and SARS-CoV-2 Variants
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Self-citation
Metadata
- 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
- 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
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