학술논문

Broadly neutralizing antibodies target the coronavirus fusion peptide.
Document Type
Article
Source
Science. 8/12/2022, Vol. 377 Issue 6607, p728-735. 8p. 5 Color Photographs.
Subject
*IMMUNOGLOBULINS
*CORONAVIRUSES
*SARS disease
*CORONAVIRUS diseases
*MONOCLONAL antibodies
Language
ISSN
0036-8075
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. [ABSTRACT FROM AUTHOR]