An antibody class with a common CDRH3 motif broadly neutralizes sarbecoviruses.

Publication Type:

Journal Article

Source:

Sci Transl Med, p.eabn6859 (2022)

Abstract:

<p>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.</p>

PDB: 
7SD5, 7SI2, 7TTM, 7TTX, and 7TTY
Detector: 
EIGER
EIGER2
Beamline: 
24-ID-C
24-ID-E
7TTM