Defining variant-resistant epitopes targeted by SARS-CoV-2 antibodies: A global consortium study

Abstract

Antibody-based therapeutics and vaccines are essential to combat COVID-19 morbidity and mortality following severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. Multiple mutations in SARS-CoV-2 that could impair antibody defenses propagated in human-to-human transmission and spillover/spillback events between humans and animals. To develop prevention and therapeutic strategies, we formed an international consortium to map the epitope landscape on the SARS-CoV-2 Spike, defining and structurally illustrating seven receptor-binding domain (RBD)-directed antibody communities with distinct footprints and competition profiles. Pseudovirion-based neutralization assays reveal Spike mutations, individually and clustered together in variants, that impact antibody function among the communities. Key classes of RBD-targeted antibodies maintain neutralization activity against these emerging SARS-CoV-2 variants. These results provide a framework for selecting antibody treatment cocktails and understanding how viral variants might affect antibody therapeutic efficacy.