Comprehensive mapping of mutations to the SARS-CoV-2 receptor-binding domain that affect recognition by polyclonal human serum antibodies

By Allison J. Greaney, Andrea N. Loes, K. H. Crawford, Tyler N. Starr, Keara D. Malone, H. Chu, Jesse D. Bloom. bioRxiv, 2021

749 citations recorded by the source corpus.

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.

Subfields: Infectious Diseases, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/fd6ebb8b7498c0401ac0e7b0107b75705bf55b0b

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Citations in the corpus

Emergence of SARS-CoV-2 B.1.1.7 Lineage — United States, December 29, 2020–January 12, 2021 (2021, background): “A recent case report documented the first case of SARS-CoV-2 reinfection in Brazil with a SARS-CoV-2 variant that contained the E484K mutation,** which has been shown to reduce neutralization by convalescent sera and monoclonal antibodies (9,10).”
Multiple SARS-CoV-2 variants escape neutralization by vaccine-induced humoral immunity (2021, positive): “The P.2. variant, which contains an E484K mutation within the RBD region, was capable of signiﬁcantly reducing neutralization potency of fully vaccinated individuals, in line with what has been suggested by deep mutational scanning (Greaney et al., 2021a; Jangra et al., 2021).”
A human coronavirus evolves antigenically to escape antibody immunity (2020, background): “In this respect, it is worth noting that while the neutralizing activity of SARS-CoV-2 immunity elicited by infection primarily targets the RBD [36,54], mutations to the NTD also reduce neutralization by some antibodies and sera [55–62]—and some regions of the NTD undergo significant sequence evolut”
Genomics and epidemiology of the P.1 SARS-CoV-2 lineage in Manaus, Brazil (2021, background): “Moreover, E484K is associated with reduced antibody neutralisation (6, 56-58).”