Broadly neutralizing antibodies target the coronavirus fusion peptide

Science. 2022 Aug 12;377(6607):728-735. doi: 10.1126/science.abq3773. Epub 2022 Jul 12.

Abstract

The potential for future coronavirus outbreaks highlights the need to broadly target this group of pathogens. We used an epitope-agnostic approach to identify six monoclonal antibodies that bind to spike proteins from all seven human-infecting coronaviruses. All six antibodies target the conserved fusion peptide region adjacent to the S2' cleavage site. COV44-62 and COV44-79 broadly neutralize alpha- and betacoronaviruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron subvariants BA.2 and BA.4/5, albeit with lower potency than receptor binding domain-specific antibodies. In crystal structures of COV44-62 and COV44-79 antigen-binding fragments with the SARS-CoV-2 fusion peptide, the fusion peptide epitope adopts a helical structure and includes the arginine residue at the S2' cleavage site. COV44-79 limited disease caused by SARS-CoV-2 in a Syrian hamster model. These findings highlight the fusion peptide as a candidate epitope for next-generation coronavirus vaccine development.

MeSH terms

  • Antibodies, Monoclonal* / immunology
  • Antibodies, Viral* / immunology
  • Broadly Neutralizing Antibodies* / immunology
  • COVID-19 Vaccines / chemistry
  • COVID-19 Vaccines / immunology
  • COVID-19* / immunology
  • COVID-19* / prevention & control
  • Epitopes* / chemistry
  • Epitopes* / immunology
  • Humans
  • Peptides / immunology
  • Protein Conformation, alpha-Helical
  • Protein Domains
  • SARS-CoV-2* / immunology
  • Spike Glycoprotein, Coronavirus* / chemistry
  • Spike Glycoprotein, Coronavirus* / immunology

Substances

  • Antibodies, Monoclonal
  • Antibodies, Viral
  • Broadly Neutralizing Antibodies
  • COVID-19 Vaccines
  • Epitopes
  • Peptides
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2