Back to Search
Start Over
An antibody targeting the N-terminal domain of SARS-CoV-2 disrupts the spike trimer
- Source :
- Journal of Clinical Investigation. June 1, 2022, Vol. 132 Issue 11
- Publication Year :
- 2022
-
Abstract
- The protective human antibody response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) focuses on the spike (S) protein, which decorates the virion surface and mediates cell binding and entry. Most SARS-CoV-2 protective antibodies target the receptor-binding domain or a single dominant epitope ('supersite') on the N-terminal domain (NTD). Using the single B cell technology called linking B cell receptor to antigen specificity through sequencing (LIBRASeq), we isolated a large panel of NTD-reactive and SARS-CoV-2-neutralizing antibodies from an individual who had recovered from COVID-19. We found that neutralizing antibodies against the NTD supersite were commonly encoded by the IGHV1-24 gene, forming a genetic cluster representing a public B cell clonotype. However, we also discovered a rare human antibody, COV23434, that recognizes a site of vulnerability on the SARS-CoV-2 S protein in the trimer interface (TI) and possesses a distinct class of functional activity. COV2-3434 disrupted the integrity of S protein trimers, inhibited the cell-to-cell spread of the virus in culture, and conferred protection in human angiotensin-converting enzyme 2-transgenic (ACE2-transgenic) mice against the SARS-CoV-2 challenge. This study provides insight into antibody targeting of the S protein TI region, suggesting this region may be a site of virus vulnerability.<br />Introduction During the COVID-19 pandemic, more than 150 vaccine candidates were developed, but only a few have been licensed. Most licensed vaccines encode the full-length spike (S) protein, including 2 [...]
Details
- Language :
- English
- ISSN :
- 00219738
- Volume :
- 132
- Issue :
- 11
- Database :
- Gale General OneFile
- Journal :
- Journal of Clinical Investigation
- Publication Type :
- Academic Journal
- Accession number :
- edsgcl.706296503
- Full Text :
- https://doi.org/10.1172/JCI159062