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.
Highlights
Neutralizing antibodies against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike are associated with protection against infection in both humans (Addetia et al, 2020; Lumley et al, 2020) and animals (Alsoussi et al, 2020; Walls et al, 2020; Zost et al, 2020a)
receptor-binding domain (RBD)-targeting antibodies dominate the neutralizing activity of most convalescent plasma We characterized 35 plasma samples longitudinally collected from 17 different SARS-CoV-2-infected individuals between 15 and 152 days post-symptom onset (Figure S1A)
Prior work has shown that these samples all have RBD-binding antibodies and neutralizing activity, with a median neutralization titer 50% (NT50) of $250 against lentiviral particles pseudotyped with the D614 variant of the SARS-CoV-2 spike
Summary
Neutralizing antibodies against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike are associated with protection against infection in both humans (Addetia et al, 2020; Lumley et al, 2020) and animals (Alsoussi et al, 2020; Walls et al, 2020; Zost et al, 2020a). Several recent studies have identified viral mutations that impact neutralization by polyclonal human plasma or sera These studies have relied on either selecting viral escape mutants with reduced neutralization sensitivity (Andreano et al, 2020; Weisblum et al, 2020) or characterizing the antigenic effects of specific mutations such as those observed in circulating viral isolates (Kemp et al, 2020b; Li et al, 2020; Liu et al, 2020b; Thomson et al, 2020; Wang et al, 2021; Wibmer et al, 2021). This work has shown that single mutations to the spike’s receptor-binding domain (RBD) or N-terminal domain (NTD) can appreciably reduce viral neutralization by polyclonal plasma, sometimes by as much as 10fold These studies characterize an incomplete subset of all possible mutations and do not completely describe the effects of viral mutations on recognition by polyclonal antibodies
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