Cell Host & Microbe
Volume 29, Issue 3, 10 March 2021, Pages 463-476.e6
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Article
Comprehensive mapping of mutations in the SARS-CoV-2 receptor-binding domain that affect recognition by polyclonal human plasma antibodies

https://doi.org/10.1016/j.chom.2021.02.003Get rights and content
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Highlights

  • Comprehensively map all RBD mutations that reduce human polyclonal plasma binding

  • Identify common RBD epitopes as well as heterogeneity within and between individuals

  • Validate polyclonal plasma-escape mutations in neutralization assays

  • Mutations with large effects such as E484K are present in circulating isolates

Summary

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

SARS-CoV-2
spike
receptor-binding domain
RBD
polyclonal immunity
antibody escape
deep mutational scanning

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