An antibody class with a common CDRH3 motif broadly neutralizes sarbecoviruses

Sci Transl Med. 2022 May 25;14(646):eabn6859. doi: 10.1126/scitranslmed.abn6859. Epub 2022 May 25.


The devastation caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has made clear the importance of pandemic preparedness. To address future zoonotic outbreaks due to related viruses in the sarbecovirus subgenus, we identified a human monoclonal antibody, 10-40, that neutralized or bound all sarbecoviruses tested in vitro and protected against SARS-CoV-2 and SARS-CoV in vivo. Comparative studies with other receptor-binding domain (RBD)-directed antibodies showed 10-40 to have the greatest breadth against sarbecoviruses, suggesting that 10-40 is a promising agent for pandemic preparedness. Moreover, structural analyses on 10-40 and similar antibodies not only defined an epitope cluster in the inner face of the RBD that is well conserved among sarbecoviruses but also uncovered a distinct antibody class with a common CDRH3 motif. Our analyses also suggested that elicitation of this class of antibodies may not be overly difficult, an observation that bodes well for the development of a pan-sarbecovirus vaccine.

Publication types

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

MeSH terms

  • Antibodies, Viral
  • COVID-19*
  • Humans
  • Immunoglobulin Isotypes
  • SARS-CoV-2*
  • Spike Glycoprotein, Coronavirus


  • Antibodies, Viral
  • Immunoglobulin Isotypes
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2