Back to Search
Start Over
Rare, convergent antibodies targeting the stem helix broadly neutralize diverse betacoronaviruses.
- Source :
- Cell Host & Microbe; Jan2023, Vol. 31 Issue 1, p97-97, 1p
- Publication Year :
- 2023
-
Abstract
- Humanity has faced three recent outbreaks of novel betacoronaviruses, emphasizing the need to develop approaches that broadly target coronaviruses. Here, we identify 55 monoclonal antibodies from COVID-19 convalescent donors that bind diverse betacoronavirus spike proteins. Most antibodies targeted an S2 epitope that included the K814 residue and were non-neutralizing. However, 11 antibodies targeting the stem helix neutralized betacoronaviruses from different lineages. Eight antibodies in this group, including the six broadest and most potent neutralizers, were encoded by IGHV1-46 and IGKV3-20. Crystal structures of three antibodies of this class at 1.5–1.75-Å resolution revealed a conserved mode of binding. COV89-22 neutralized SARS-CoV-2 variants of concern including Omicron BA.4/5 and limited disease in Syrian hamsters. Collectively, these findings identify a class of IGHV1-46/IGKV3-20 antibodies that broadly neutralize betacoronaviruses by targeting the stem helix but indicate these antibodies constitute a small fraction of the broadly reactive antibody response to betacoronaviruses after SARS-CoV-2 infection. [Display omitted] • Isolation of 55 broadly reactive monoclonal antibodies to betacoronaviruses • Only a minority are broadly neutralizing and target the stem helix • Identification of an IGHV1-46/IGKV3-20 gene signature of the broad neutralizers • Structures of IGHV1-46/IGKV3-20 antibodies reveal a conserved mode of binding The characteristics of antibodies that broadly neutralize coronaviruses are poorly understood. Here, Dacon et al. identify a class of stem helix-specific monoclonal antibodies from COVID-19 convalescent donors that neutralize diverse betacoronaviruses, use an IGHV1-46/IGKV3-20 gene signature, and bind in a conserved manner to the spike protein. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 19313128
- Volume :
- 31
- Issue :
- 1
- Database :
- Supplemental Index
- Journal :
- Cell Host & Microbe
- Publication Type :
- Academic Journal
- Accession number :
- 161172009
- Full Text :
- https://doi.org/10.1016/j.chom.2022.10.010