A structure-function analysis shows SARS-CoV-2 BA.2.86 balances antibody escape and ACE2 affinity

DOI: 10.1016/j.xcrm.2024.101553

Authors: Chang Liu (Centre for Human Genetics, University of Oxford; Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford) , Daming Zhou (Centre for Human Genetics, University of Oxford; Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford) , Aiste Dijokaite-Guraliuc (Centre for Human Genetics, University of Oxford) , Piyada Supasa (Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford) , Helen M. E. Duyvesteyn (Centre for Human Genetics, University of Oxford) , Helen M. Ginn (Centre for Free Electron Laser Science) , Muneeswaran Selvaraj (Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford) , Alexander J. Mentzer (Centre for Human Genetics, University of Oxford; NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust) , Raksha Das (Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford) , Thushan I. De Silva (University of Sheffield; Sheffield Teaching Hospitals NHS Foundation Trust) , Thomas G. Ritter (NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust) , Megan Plowright (Sheffield Teaching Hospitals NHS Foundation Trust) , Thomas A.h. Newman (Sheffield Teaching Hospitals NHS Foundation Trust) , Lizzie Stafford (NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust) , Barbara Kronsteiner (University of Oxford) , Nigel Temperton (University of Kent and University of Greenwich Chatham Maritime) , Yuan Lui (John Radcliffe Hospital, University of Oxford) , Martin Fellermeyer (John Radcliffe Hospital, University of Oxford) , Philip Goulder (University of Oxford) , Paul Klenerman (NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust; University of Oxford) , Susanna J. Dunachie (NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust; University of Oxford) , Michael I. Barton (Diamond Light Source) , Mikhail A. Kutuzov (Diamond Light Source) , Omer Dushek (Diamond Light Source) , Elizabeth E. Fry (Centre for Human Genetics, University of Oxford) , Juthathip Mongkolsapaya (Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford; Centre for Human Genetics, University of Oxford; Mahidol University) , Jingshan Ren (Centre for Human Genetics, University of Oxford) , David I. Stuart (Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford; Centre for Human Genetics, University of Oxford) , Gavin R. Screaton (Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford; Centre for Human Genetics, University of Oxford)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Cell Reports Medicine , VOL 376

State: Published (Approved)
Published: May 2024
Diamond Proposal Number(s): 28534 , 27009

Abstract: BA.2.86, a recently described sublineage of SARS-CoV-2 Omicron, contains many mutations in the spike gene. It appears to have originated from BA.2 and is distinct from the XBB variants responsible for many infections in 2023. The global spread and plethora of mutations in BA.2.86 has caused concern that it may possess greater immune-evasive potential, leading to a new wave of infection. Here, we examine the ability of BA.2.86 to evade the antibody response to infection using a panel of vaccinated or naturally infected sera and find that it shows marginally less immune evasion than XBB.1.5. We locate BA.2.86 in the antigenic landscape of recent variants and look at its ability to escape panels of potent monoclonal antibodies generated against contemporary SARS-CoV-2 infections. We demonstrate, and provide a structural explanation for, increased affinity of BA.2.86 to ACE2, which may increase transmissibility.

Diamond Keywords: COVID-19; Viruses

Subject Areas: Biology and Bio-materials


Instruments: I03-Macromolecular Crystallography

Added On: 13/05/2024 08:22

Documents:
PIIS2666379124002453.pdf

Discipline Tags:

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

Technical Tags:

Diffraction Macromolecular Crystallography (MX)