Prospective mapping of viral mutations that escape antibodies used to treat COVID-19

Science. 2021 Feb 19;371(6531):850-854. doi: 10.1126/science.abf9302. Epub 2021 Jan 25.

Abstract

Antibodies are a potential therapy for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but the risk of the virus evolving to escape them remains unclear. Here we map how all mutations to the receptor binding domain (RBD) of SARS-CoV-2 affect binding by the antibodies in the REGN-COV2 cocktail and the antibody LY-CoV016. These complete maps uncover a single amino acid mutation that fully escapes the REGN-COV2 cocktail, which consists of two antibodies, REGN10933 and REGN10987, targeting distinct structural epitopes. The maps also identify viral mutations that are selected in a persistently infected patient treated with REGN-COV2 and during in vitro viral escape selections. Finally, the maps reveal that mutations escaping the individual antibodies are already present in circulating SARS-CoV-2 strains. These complete escape maps enable interpretation of the consequences of mutations observed during viral surveillance.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Substitution
  • Angiotensin-Converting Enzyme 2 / metabolism
  • Antibodies, Monoclonal, Humanized / immunology*
  • Antibodies, Monoclonal, Humanized / metabolism
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Antibodies, Viral / immunology*
  • Antibodies, Viral / metabolism
  • Antibodies, Viral / therapeutic use
  • COVID-19 / therapy*
  • Cells, Cultured
  • Drug Combinations
  • Humans
  • Immunization, Passive
  • Mutation*
  • Protein Binding
  • Protein Domains
  • Receptors, Coronavirus / metabolism
  • SARS-CoV-2 / genetics*
  • SARS-CoV-2 / immunology*
  • Spike Glycoprotein, Coronavirus / chemistry
  • Spike Glycoprotein, Coronavirus / genetics*
  • Spike Glycoprotein, Coronavirus / immunology*
  • Spike Glycoprotein, Coronavirus / metabolism

Substances

  • Antibodies, Monoclonal, Humanized
  • Antibodies, Viral
  • Drug Combinations
  • Receptors, Coronavirus
  • Spike Glycoprotein, Coronavirus
  • casirivimab and imdevimab drug combination
  • spike protein, SARS-CoV-2
  • imdevimab
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2
  • casirivimab
  • etesevimab

Supplementary concepts

  • COVID-19 serotherapy