Comprehensive mapping of mutations in the SARS-CoV-2 receptor-binding domain that affect recognition by polyclonal human plasma antibodies
- PMID: 33592168
- PMCID: PMC7869748
- DOI: 10.1016/j.chom.2021.02.003
Comprehensive mapping of mutations in the SARS-CoV-2 receptor-binding domain that affect recognition by polyclonal human plasma antibodies
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 plasma antibodies are impacted by all mutations to the spike's receptor-binding domain (RBD), the main target of plasma neutralizing activity. Binding by polyclonal plasma antibodies is affected by mutations in three main epitopes in the RBD, but longitudinal samples reveal that the impact of these mutations on antibody binding varies substantially 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 plasma is reduced >10-fold by several mutations, including one in the emerging 20H/501Y.V2 and 20J/501Y.V3 SARS-CoV-2 lineages. Going forward, these plasma escape maps can inform surveillance of SARS-CoV-2 evolution.
Keywords: RBD; SARS-CoV-2; antibody escape; deep mutational scanning; polyclonal immunity; receptor-binding domain; spike.
Copyright © 2021 Elsevier Inc. All rights reserved.
Conflict of interest statement
Declaration of interests H.Y.C. is a consultant for Merck, Pfizer, Ellume, and Bill and Melinda Gates Foundation and has received support from Cepheid and Sanofi-Pasteur. The other authors declare no competing interests.
Figures
Similar articles
-
Structural and antigenic variations in the spike protein of emerging SARS-CoV-2 variants.PLoS Pathog. 2022 Feb 17;18(2):e1010260. doi: 10.1371/journal.ppat.1010260. eCollection 2022 Feb. PLoS Pathog. 2022. PMID: 35176090 Free PMC article. Review.
-
Comprehensive mapping of binding hot spots of SARS-CoV-2 RBD-specific neutralizing antibodies for tracking immune escape variants.Genome Med. 2021 Oct 14;13(1):164. doi: 10.1186/s13073-021-00985-w. Genome Med. 2021. PMID: 34649620 Free PMC article.
-
Mapping mutations to the SARS-CoV-2 RBD that escape binding by different classes of antibodies.Nat Commun. 2021 Jul 7;12(1):4196. doi: 10.1038/s41467-021-24435-8. Nat Commun. 2021. PMID: 34234131 Free PMC article.
-
Escape from neutralizing antibodies by SARS-CoV-2 spike protein variants.Elife. 2020 Oct 28;9:e61312. doi: 10.7554/eLife.61312. Elife. 2020. PMID: 33112236 Free PMC article.
-
Recognition of the SARS-CoV-2 receptor binding domain by neutralizing antibodies.Biochem Biophys Res Commun. 2021 Jan 29;538:192-203. doi: 10.1016/j.bbrc.2020.10.012. Epub 2020 Oct 10. Biochem Biophys Res Commun. 2021. PMID: 33069360 Free PMC article. Review.
Cited by
-
PRIEST: predicting viral mutations with immune escape capability of SARS-CoV-2 using temporal evolutionary information.Brief Bioinform. 2024 Mar 27;25(3):bbae218. doi: 10.1093/bib/bbae218. Brief Bioinform. 2024. PMID: 38742520 Free PMC article.
-
Nanobody repertoire generated against the spike protein of ancestral SARS-CoV-2 remains efficacious against the rapidly evolving virus.Elife. 2024 May 7;12:RP89423. doi: 10.7554/eLife.89423. Elife. 2024. PMID: 38712823 Free PMC article.
-
Proactive vaccination using multiviral Quartet Nanocages to elicit broad anti-coronavirus responses.Nat Nanotechnol. 2024 May 6. doi: 10.1038/s41565-024-01655-9. Online ahead of print. Nat Nanotechnol. 2024. PMID: 38710880
-
Mapping immunodominant sites on the MERS-CoV spike glycoprotein targeted by infection-elicited antibodies in humans.bioRxiv [Preprint]. 2024 Apr 2:2024.03.31.586409. doi: 10.1101/2024.03.31.586409. bioRxiv. 2024. PMID: 38617298 Free PMC article. Preprint.
-
T and B cell epitope analysis for the immunogenicity evaluation and mitigation of antibody-based therapeutics.MAbs. 2024 Jan-Dec;16(1):2324836. doi: 10.1080/19420862.2024.2324836. Epub 2024 Mar 21. MAbs. 2024. PMID: 38512798 Free PMC article. Review.
References
-
- Addetia A., Crawford K.H.D., Dingens A., Zhu H., Roychoudhury P., Huang M.-L., Jerome K.R., Bloom J.D., Greninger A.L. Neutralizing Antibodies Correlate with Protection from SARS-CoV-2 in Humans during a Fishery Vessel Outbreak with a High Attack Rate. J. Clin. Microbiol. 2020 doi: 10.1128/JCM.02107-20. - DOI - PMC - PubMed
-
- Barnes C.O., West A.P., Jr., Huey-Tubman K.E., Hoffmann M.A.G., Sharaf N.G., Hoffman P.R., Koranda N., Gristick H.B., Gaebler C., Muecksch F., et al. Structures of Human Antibodies Bound to SARS-CoV-2 Spike Reveal Common Epitopes and Recurrent Features of Antibodies. Cell. 2020;182:828–842.e16. - PMC - PubMed
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Miscellaneous