A neutralizing epitope on the SD1 domain of SARS-CoV-2 spike targeted following infection and vaccination
Year: 2022
Type: article
Abstract: 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.
Source: Cell Reports
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $5,200
Funders: King’s College London, Wellcome Trust, Francis Crick Institute, King's College Hospital NHS Foundation Trust, Cancer Research UK, National Institute for Health and Care Research, Leverhulme Trust, Department of Health and Social Care, King's College London, European Commission, Huo Family Foundation, Medical Research Council, Engineering and Physical Sciences Research Council, European and Developing Countries Clinical Trials Partnership
Awards: G1757733276, Flow Cytometry for Investigating HIV Infection of Living Cells, G2647684415, Interferon and MX2 Mediated Control of HIV-1., A London consortium to establish a high resolution cryo-electron microscopy facility for research and training, G5074405104, G5494735139, G2P-UK; A National Virology Consortium to address phenotypic consequences of SARSCoV-2 genomic variation, G6795691369, Mapping membrane protein dynamics in time and space with mass spectrometry, Investigating COVID-19 infectiousness and antibody evolution in COVID-19 patients in SSA and Europe, G7493511746, G7499770399, Interferon and Human Pandemic Viruses
OpenAlex ID: W4292425691