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

Tyler N Starr; Allison J Greaney; Amin Addetia; William W Hannon; Manish C Choudhary; Adam S Dingens; Jonathan Z Li; Jesse D Bloom

doi:10.1126/science.abf9302

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.

Authors

Tyler N Starr^#¹, Allison J Greaney^#^{1

2

3}, Amin Addetia^{1

4}, William W Hannon^{1

4}, Manish C Choudhary⁵, Adam S Dingens¹, Jonathan Z Li⁵, Jesse D Bloom^{6

2

7}

Affiliations

¹ Basic Sciences and Computational Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
² Department of Genome Sciences, University of Washington, Seattle, WA 98109, USA.
³ Medical Scientist Training Program, University of Washington, Seattle, WA 98109, USA.
⁴ Molecular and Cellular Biology Graduate Program, University of Washington, Seattle, WA 98109, USA.
⁵ Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
⁶ Basic Sciences and Computational Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA. jbloom@fredhutch.org.
⁷ Howard Hughes Medical Institute, Seattle, WA 98109, USA.

^# Contributed equally.

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*
COVID-19 Serotherapy
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

Abstract

Publication types

MeSH terms

Substances

Grants and funding