PT - JOURNAL ARTICLE AU - Greaney, Allison J. AU - Loes, Andrea N. AU - Crawford, Katharine H.D. AU - Starr, Tyler N. AU - Malone, Keara D. AU - Chu, Helen Y. AU - Bloom, Jesse D. TI - Comprehensive mapping of mutations to the SARS-CoV-2 receptor-binding domain that affect recognition by polyclonal human serum antibodies AID - 10.1101/2020.12.31.425021 DP - 2021 Jan 01 TA - bioRxiv PG - 2020.12.31.425021 4099 - http://biorxiv.org/content/early/2021/01/04/2020.12.31.425021.short 4100 - http://biorxiv.org/content/early/2021/01/04/2020.12.31.425021.full 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.