Tweet
J Clin Invest
. 2022 Apr 26;e159062.
doi: 10.1172/JCI159062. Online ahead of print.
An antibody targeting the N-terminal domain of SARS-CoV-2 disrupts the spike trimer
Naveenchandra Suryadevara 1 , Andrea R Shiakolas 2 , Laura A VanBlargan 3 , Elad Binshtein 1 , Rita E Chen 3 , James Brett Case 3 , Kevin J Kramer 2 , Erica C Armstrong 1 , Luke Myers 1 , Andrew Trivette 1 , Christopher Gainza 1 , Rachel S Nargi 1 , Christopher N Selverian 4 , Edgar Davidson 5 , Benjamin J Doranz 6 , Summer M Diaz 1 , Laura S Handal 1 , Robert H Carnahan 7 , Michael S Diamond 3 , Ivelin S Georgiev 1 , James E Crowe Jr 1
Affiliations
- PMID: 35472136
- DOI: 10.1172/JCI159062
Abstract
The protective human antibody response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus 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). Here, using the single B cell technology LIBRA-seq, 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 to the NTD supersite commonly are encoded by the IGHV1-24 gene, forming a genetic cluster that represents a public B cell clonotype. However, we also discovered a rare human antibody, COV2-3434, that recognizes a site of vulnerability on the SARS-CoV-2 S protein in the trimer interface and possesses a distinct class of functional activity. COV2-3434 disrupted the integrity of S protein trimers, inhibited cell-to-cell spread of virus in culture, and conferred protection in human ACE2 transgenic mice against SARS-CoV-2 challenge. This study provides insight about antibody targeting of the S protein trimer interface region, suggesting this region may be a site of virus vulnerability.
Keywords: Adaptive immunity; Antigen; Immunoglobulins; Immunology; Virology.