Cross-neutralization of SARS-CoV-2 by a human monoclonal SARS-CoV antibody

Nature. 2020 Jul;583(7815):290-295. doi: 10.1038/s41586-020-2349-y. Epub 2020 May 18.

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a newly emerged coronavirus that is responsible for the current pandemic of coronavirus disease 2019 (COVID-19), which has resulted in more than 3.7 million infections and 260,000 deaths as of 6 May 20201,2. Vaccine and therapeutic discovery efforts are paramount to curb the pandemic spread of this zoonotic virus. The SARS-CoV-2 spike (S) glycoprotein promotes entry into host cells and is the main target of neutralizing antibodies. Here we describe several monoclonal antibodies that target the S glycoprotein of SARS-CoV-2, which we identified from memory B cells of an individual who was infected with severe acute respiratory syndrome coronavirus (SARS-CoV) in 2003. One antibody (named S309) potently neutralizes SARS-CoV-2 and SARS-CoV pseudoviruses as well as authentic SARS-CoV-2, by engaging the receptor-binding domain of the S glycoprotein. Using cryo-electron microscopy and binding assays, we show that S309 recognizes an epitope containing a glycan that is conserved within the Sarbecovirus subgenus, without competing with receptor attachment. Antibody cocktails that include S309 in combination with other antibodies that we identified further enhanced SARS-CoV-2 neutralization, and may limit the emergence of neutralization-escape mutants. These results pave the way for using S309 and antibody cocktails containing S309 for prophylaxis in individuals at a high risk of exposure or as a post-exposure therapy to limit or treat severe disease.

Publication types

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

MeSH terms

  • Angiotensin-Converting Enzyme 2
  • Animals
  • Antibodies, Monoclonal / chemistry
  • Antibodies, Monoclonal / immunology*
  • Antibodies, Monoclonal / pharmacology
  • Antibodies, Neutralizing / chemistry
  • Antibodies, Neutralizing / immunology*
  • Antibodies, Neutralizing / pharmacology
  • Antibodies, Viral / chemistry
  • Antibodies, Viral / immunology
  • Antibodies, Viral / pharmacology
  • Antibody-Dependent Cell Cytotoxicity / drug effects
  • Antibody-Dependent Cell Cytotoxicity / immunology
  • B-Lymphocytes / immunology
  • Betacoronavirus / chemistry
  • Betacoronavirus / drug effects
  • Betacoronavirus / immunology*
  • COVID-19
  • Chlorocebus aethiops
  • Coronavirus Infections / immunology
  • Coronavirus Infections / prevention & control
  • Coronavirus Infections / therapy
  • Coronavirus Infections / virology
  • Cross Reactions / drug effects
  • Cross Reactions / immunology*
  • Cryoelectron Microscopy
  • Epitopes, B-Lymphocyte / chemistry
  • Epitopes, B-Lymphocyte / immunology
  • HEK293 Cells
  • Humans
  • Immune Evasion / immunology
  • Immunoglobulin Fab Fragments / chemistry
  • Immunoglobulin Fab Fragments / immunology
  • Immunoglobulin Fab Fragments / pharmacology
  • Immunologic Memory / immunology
  • Killer Cells, Natural / drug effects
  • Killer Cells, Natural / immunology
  • Models, Molecular
  • Neutralization Tests
  • Pandemics / prevention & control
  • Peptidyl-Dipeptidase A / chemistry
  • Peptidyl-Dipeptidase A / metabolism
  • Pneumonia, Viral / immunology
  • Pneumonia, Viral / prevention & control
  • Pneumonia, Viral / therapy
  • Pneumonia, Viral / virology
  • SARS Virus / chemistry
  • SARS Virus / drug effects
  • SARS Virus / immunology*
  • SARS-CoV-2
  • Severe Acute Respiratory Syndrome / immunology*
  • Severe Acute Respiratory Syndrome / virology
  • Spike Glycoprotein, Coronavirus / chemistry
  • Spike Glycoprotein, Coronavirus / immunology*
  • Vero Cells

Substances

  • Antibodies, Monoclonal
  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Epitopes, B-Lymphocyte
  • Immunoglobulin Fab Fragments
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2
  • Peptidyl-Dipeptidase A
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2