학술논문
Potent neutralization of SARS-CoV-2 variants of concern by an antibody with an uncommon genetic signature and structural mode of spike recognition
Document Type
article
Author
Kevin J. Kramer; Nicole V. Johnson; Andrea R. Shiakolas; Naveenchandra Suryadevara; Sivakumar Periasamy; Nagarajan Raju; Jazmean K. Williams; Daniel Wrapp; Seth J. Zost; Lauren M. Walker; Steven C. Wall; Clinton M. Holt; Ching-Lin Hsieh; Rachel E. Sutton; Ariana Paulo; Rachel S. Nargi; Edgar Davidson; Benjamin J. Doranz; James E. Crowe, Jr.; Alexander Bukreyev; Robert H. Carnahan; Jason S. McLellan; Ivelin S. Georgiev
Source
Cell Reports, Vol 37, Iss 1, Pp 109784- (2021)
Subject
Language
English
ISSN
2211-1247
Abstract
Summary: The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lineages that are more transmissible and resistant to currently approved antibody therapies poses a considerable challenge to the clinical treatment of coronavirus disease (COVID-19). Therefore, the need for ongoing discovery efforts to identify broadly reactive monoclonal antibodies to SARS-CoV-2 is of utmost importance. Here, we report a panel of SARS-CoV-2 antibodies isolated using the linking B cell receptor to antigen specificity through sequencing (LIBRA-seq) technology from an individual who recovered from COVID-19. Of these antibodies, 54042-4 shows potent neutralization against authentic SARS-CoV-2 viruses, including variants of concern (VOCs). A cryoelectron microscopy (cryo-EM) structure of 54042-4 in complex with the SARS-CoV-2 spike reveals an epitope composed of residues that are highly conserved in currently circulating SARS-CoV-2 lineages. Further, 54042-4 possesses uncommon genetic and structural characteristics that distinguish it from other potently neutralizing SARS-CoV-2 antibodies. Together, these findings provide motivation for the development of 54042-4 as a lead candidate to counteract current and future SARS-CoV-2 VOCs.