The SARS-CoV-2 neutralizing antibody response to SD1 and its evasion by BA.2.86

DOI: 10.1038/s41467-024-46982-6

Authors: Daming Zhou (Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford) , Piyada Supasa (Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford) , Chang Liu (Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford) , Aiste Dijokaite-Guraliuc (University of Oxford) , Helen M. E. Duyvesteyn (University of Oxford) , Muneeswaran Selvaraj (University of Oxford) , Alexander J. Mentzer (University of Oxford; Oxford University Hospitals NHS Foundation Trust) , Raksha Das (University of Oxford) , Wanwisa Dejnirattisai (Mahidol University) , Nigel Temperton (University of Kent and Greenwich Chatham Maritime) , Paul Klenerman (Oxford University Hospitals NHS Foundation Trust; University of Oxford) , Susanna J. Dunachie (Oxford University Hospitals NHS Foundation Trust; University of Oxford; Mahidol-Oxford Tropical Medicine Research Unit) , Elizabeth E. Fry (University of Oxford) , Juthathip Mongkolsapaya (Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford; Mahidol-Oxford Tropical Medicine Research Unit) , Jingshan Ren (University of Oxford) , David I. Stuart (Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford; Diamond Light Source) , Gavin R. Screaton (Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Nature Communications , VOL 15

State: Published (Approved)
Published: March 2024

Abstract: Under pressure from neutralising antibodies induced by vaccination or infection the SARS-CoV-2 spike gene has become a hotspot for evolutionary change, leading to the failure of all mAbs developed for clinical use. Most potent antibodies bind to the receptor binding domain which has become heavily mutated. Here we study responses to a conserved epitope in sub-domain-1 (SD1) of spike which have become more prominent because of mutational escape from antibodies directed to the receptor binding domain. Some SD1 reactive mAbs show potent and broad neutralization of SARS-CoV-2 variants. We structurally map the dominant SD1 epitope and provide a mechanism of action by blocking interaction with ACE2. Mutations in SD1 have not been sustained to date, but one, E554K, leads to escape from mAbs. This mutation has now emerged in several sublineages including BA.2.86, reflecting selection pressure on the virus exerted by the increasing prominence of the anti-SD1 response.

Diamond Keywords: COVID-19; Viruses

Subject Areas: Biology and Bio-materials


Technical Areas:

Added On: 31/03/2024 10:33

Documents:
s41467-024-46982-6.pdf

Discipline Tags:

Pathogens Infectious Diseases Health & Wellbeing Structural biology Life Sciences & Biotech

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