RT Journal Article
SR Electronic
T1 Comprehensive mapping of mutations to the SARS-CoV-2 receptor-binding domain that affect recognition by polyclonal human serum antibodies
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.12.31.425021
DO 10.1101/2020.12.31.425021
A1 Allison J. Greaney
A1 Andrea N. Loes
A1 Katharine H.D. Crawford
A1 Tyler N. Starr
A1 Keara D. Malone
A1 Helen Y. Chu
A1 Jesse D. Bloom
YR 2021
UL http://biorxiv.org/content/early/2021/01/04/2020.12.31.425021.abstract
AB 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.Competing Interest StatementH.Y.C. is a consultant for Merck and Pfizer and receives research funds from Cepheid, Ellume, Genentech, and Sanofi-Pasteur. The other authors declare no competing interests.