A neutralizing epitope on the SD1 domain of SARS-CoV-2 spike targeted following infection and vaccination

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike is the target for neutralizing antibodies elicited following both infection and vaccination. While extensive research has shown that the receptor binding domain (RBD) and, to a lesser extent, the N-terminal domain (NTD) are the predo...

Full description

Saved in:
Bibliographic Details
Published in:Cell reports (Cambridge) Vol. 40; no. 8; p. 111276
Main Authors: Seow, Jeffrey, Khan, Hataf, Rosa, Annachiara, Calvaresi, Valeria, Graham, Carl, Pickering, Suzanne, Pye, Valerie E., Cronin, Nora B., Huettner, Isabella, Malim, Michael H., Politis, Argyris, Cherepanov, Peter, Doores, Katie J.
Format: Journal Article
Language:English
Published: United States Elsevier Inc 23.08.2022
The Author(s)
Subjects:
Antibodies, Neutralizing
Antibodies, Viral
antibody
COVID-19
Cryoelectron Microscopy
cryogenic electron microscopy
Epitopes
Humans
hydrogen-deuterium exchange
Neutralization Tests
neutralizing epitope
omicron
SARS-CoV-2
Spike Glycoprotein, Coronavirus
spike subdomain 1
Syndactyly
Vaccination
hydrogen-deuterium exchange
CP: Immunology
SARS-CoV-2
spike subdomain 1
antibody
omicron
CP: Microbiology
neutralizing epitope
cryogenic electron microscopy
ISSN:2211-1247, 2211-1247
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike is the target for neutralizing antibodies elicited following both infection and vaccination. While extensive research has shown that the receptor binding domain (RBD) and, to a lesser extent, the N-terminal domain (NTD) are the predominant targets for neutralizing antibodies, identification of neutralizing epitopes beyond these regions is important for informing vaccine development and understanding antibody-mediated immune escape. Here, we identify a class of broadly neutralizing antibodies that bind an epitope on the spike subdomain 1 (SD1) and that have arisen from infection or vaccination. Using cryo-electron microscopy (cryo-EM) and hydrogen-deuterium exchange coupled to mass spectrometry (HDX-MS), we show that SD1-specific antibody P008_60 binds an epitope that is not accessible within the canonical prefusion states of the SARS-CoV-2 spike, suggesting a transient conformation of the viral glycoprotein that is vulnerable to neutralization. [Display omitted] •A neutralizing epitope on spike subdomain 1 (SD1) is identified•The SD1 epitope is conserved between current SARS-CoV-2 variants and SARS-CoV•SD1 antibodies arise from infection and vaccination•Cryo-EM reveals the SD1 epitope is occluded on many SARS-CoV-2 spike structures Seow et al. identify a class of broadly neutralizing antibodies that bind a conserved epitope on the spike subdomain 1 (SD1) and that are elicited following infection and vaccination. The SD1 epitope is occluded on spike prefusion structures, suggesting binding to a conformational state of spike.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
Present address: Faculty of Medicine, Wolfson Education Center, Hammersmith Campus, Imperial College London, Du Cane Road, London W12 0NN, UK
These authors contributed equally
Lead contact
ISSN:2211-1247
2211-1247
DOI:10.1016/j.celrep.2022.111276