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

Science. 2021 Oct 22;374(6566):472-478. doi: 10.1126/science.abh2315. Epub 2021 Sep 23.


Antibody-based therapeutics and vaccines are essential to combat COVID-19 morbidity and mortality after 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 or 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 protein, 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 affect 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Neutralizing / immunology*
  • Antibodies, Neutralizing / therapeutic use
  • Antibodies, Viral / immunology*
  • Antibodies, Viral / therapeutic use
  • Antigens, Viral / chemistry
  • Antigens, Viral / immunology
  • COVID-19 / therapy
  • Epitope Mapping*
  • Humans
  • Immunodominant Epitopes / chemistry
  • Immunodominant Epitopes / immunology*
  • Protein Binding
  • Protein Domains
  • SARS-CoV-2 / immunology*
  • Spike Glycoprotein, Coronavirus / chemistry
  • Spike Glycoprotein, Coronavirus / immunology*


  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Antigens, Viral
  • Immunodominant Epitopes
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2