The DOI matches its Crossref record; 74 of the 74 references it cites were found in a registry or an index.
Comprehensive mapping of mutations to the SARS-CoV-2 receptor-binding domain that affect recognition by polyclonal human serum antibodies
Open accessPreprint — published as 10.1016/j.chom.2021.02.003 · Paper page
Abstract
The evolution of SARS-CoV-2 could impair recognition of the virus by human antibody-mediated immunity. To facilitate prospective surveillance for such evolution, we map how convalescent serum antibodies are impacted by all mutations to the spike’s receptor-binding domain (RBD), the main target of serum neutralizing activity. Binding by polyclonal serum antibodies is affected by mutations in three main epitopes in the RBD, but there is substantial variation in the impact of mutations both among individuals and within the same individual over time. Despite this inter- and intra-person heterogeneity, the mutations that most reduce antibody binding usually occur at just a few sites in the RBD’s receptor binding motif. The most important site is E484, where neutralization by some sera is reduced >10-fold by several mutations, including one in emerging viral lineages in South Africa and Brazil. Going forward, these serum escape maps can inform surveillance of SARS-CoV-2 evolution.
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“The E484K mutation has been reported to abolish or substantially reduce neutralization by multiple potent monoclonal antibodies and polyclonal convalescent sera in both wild-type and pseudo-virus neutralization assays.12,13,17,18,22”
From Efficacy of NVX-CoV2373 Covid-19 Vaccine against the B.1.351 Variant (2021) · cites this paper as [13]
Experimental — accuracy not yet measuredIn the citing paper
“The B.1.351 variant is characterized by three deleterious mutations at key antigenic sites in the RBD, including N501Y, K417N, and E484K, with the latter two having particular functional impact.”
From Efficacy of NVX-CoV2373 Covid-19 Vaccine against the B.1.351 Variant (2021) · cites this paper as [13]
In the citing paper
“From a biological point of view, the breakthrough cases observed in this study might be due to immune evasion, mediated by particular alterations present in these strains 9,[23][24][25][26][27] .”
From Evidence for increased breakthrough rates of SARS-CoV-2 variants of concern in BNT162b2-mRNA-vaccinated individuals (2021) · cites this paper as [23]
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Cites
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Convergent Antibody Responses to SARS-CoV-2 in Convalescent Individuals
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Sorted by citations
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Widera, M., Wilhelm, A., Toptan, T., Raffel, J. M., Kowarz, E., Roesmann, F., Siemund, A. L., Luciano, V., Külp, M., Reis, J., et al. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.04.27.441606 · Cited by 2
“Further studies have shown that E484 represents an immunodominant site on the RBD since E484K reduced naturalization capacity of human convalescent sera by >100-fold (Greaney et al., 2021; Widera et al., 2021).”
BackgroundCOVID-19 does not only disturb our social rhythm
Wilde, A. A. M., & Offerhaus, J. A. (2021) · Heart Rhythm · doi:10.1016/j.hrthm.2021.02.007
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Piantadosi, A. L. (2021) · Clinical Infectious Diseases · doi:10.1093/cid/ciab224
“For example, viruses containing the spike protein mutation E484K are not neutralized as easily as wild type viruses by convalescent sera[21] or sera from vaccinated individuals[22].”
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Evaluating the Effect of SARS-CoV-2 Spike Mutations by Causal InferencePreprint
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N-terminal domain antigenic mapping reveals a site of vulnerability for SARS-CoV-2
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Voloch, C. M., Silva F, R. D., de Almeida, L. G. P., Cardoso, C. C., Brustolini, O. J., Gerber, A. L., Guimarães, A. P. D. C., Mariani, D., Costa, R. M. D., Ferreira, O. C., et al. (2020) · doi:10.1101/2020.12.23.20248598 · Cited by 372
“(8, 9) emphasize the importance of monitoring the spread of this new strain.”
Background
Metadata
- Authors
- Greaney, A. J., Loes, A. N., Crawford, K. H. D., Starr, T. N., Malone, K. D., Chu, H. Y., & Bloom, J. D.
- Affiliations
- University of Washington (US)
- Howard Hughes Medical Institute (US)
- Fred Hutch Cancer Center (US)
- Corresponding author
- Bloom, Jesse D.
- ORCID
- Venue
- Cell Host & Microbe
- Publisher
- openRxiv
- Published
- 2021-01-04
- Volume
- 29
- Issue
- 3
- Pages
- 463-476.e6
- ISSN
- 1931-3128 (ISSN-L)
- PMC
- PMC7869748
- OpenAlex
- W3127852352
- Cited by
- 1,178
- References
- 58
- Citations by year
- 2026: 43 · 2025: 64 · 2024: 79 · 2023: 158 · 2022: 361 · 2021: 459
- FWCI
- 83.77
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cell Host & Microbe (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute
- Bill and Melinda Gates Foundation (INV-004949)
- Damon Runyon Cancer Research Foundation (DRG-2381-19)
- Washington Research Foundation
- Vanderbilt University
- University of Washington
- National Institutes of Health (1s10od028685-01)
- National Institute of Allergy and Infectious Diseases (R01AI127893, T32AI083203, F30AI149928, R01AI140891, R01AI141707)
- Office of Research Infrastructure Programs, National Institutes of Health (S10OD028685)
- 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
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 detection and testing
- Keywords
- SARS-CoV-2, spike protein receptor-binding domain, antibody escape mutations, neutralizing antibodies, E484K mutation, antibody epitopes, convalescent plasma, humoral immunity
- MeSH terms
- Protein Domains, COVID-19, SARS-CoV-2, Adult, Aged, Antibodies, Monoclonal, Antibodies, Viral, Binding Sites, Cell Line, Female, Humans, Male, Middle Aged, Mutation, Prospective Studies, Protein Binding, Receptors, Virus, Young Adult, Antibodies, Neutralizing, Spike Glycoprotein, Coronavirus
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