Rapid escape of new SARS-CoV-2 Omicron variants from BA.2 directed antibody responses

DOI: 10.1016/j.celrep.2023.112271

Authors: Aiste Dijokaite-Guraliuc (Wellcome Centre for Human Genetics, University of Oxford) , Raksha Das (Wellcome Centre for Human Genetics, University of Oxford) , Daming Zhou (Wellcome Centre for Human Genetics, University of Oxford; Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford) , Helen M. Ginn (Diamond Light Source) , Chang Liu (Wellcome Centre for Human Genetics, University of Oxford; Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford) , Helen M. E. Duyvesteyn (Wellcome Centre for Human Genetics, University of Oxford) , Jiandong Huo (Wellcome Centre for Human Genetics, University of Oxford) , Rungtiwa Nutalai (Wellcome Centre for Human Genetics, University of Oxford) , Piyada Supasa (Wellcome Centre for Human Genetics, University of Oxford) , Muneeswaran Selvaraj (Wellcome Centre for Human Genetics, University of Oxford) , Thushan I. De Silva (University of Sheffield; Sheffield Teaching Hospitals NHS Foundation Trust) , Megan Plowright (University of Sheffield; Sheffield Teaching Hospitals NHS Foundation Trust) , Thomas A. H. Newman (University of Sheffield; Sheffield Teaching Hospitals NHS Foundation Trust) , Hailey Hornsby (University of Sheffield) , Alexander J. Mentzer (Wellcome Centre for Human Genetics, University of Oxford; Oxford University Hospitals NHS Foundation Trust) , Donal Skelly (Oxford University Hospitals NHS Foundation Trust; Peter Medawar Building for Pathogen Research; University of Oxford, Oxford) , Thomas G. Ritter (Oxford University Hospitals NHS Foundation Trust) , Nigel Temperton (University of Kent and Greenwich Chatham Maritime) , Paul Klenerman (Oxford University Hospitals NHS Foundation Trust; Peter Medawar Building for Pathogen Research; NIHR Oxford Biomedical Research Centre; University of Oxford) , Eleanor Barnes (Oxford University Hospitals NHS Foundation Trust; Peter Medawar Building for Pathogen Research; NIHR Oxford Biomedical Research Centre; University of Oxford) , Susanna J. Dunachie (Oxford University Hospitals NHS Foundation Trust; Peter Medawar Building for Pathogen Research; University of Oxford) , Cornelius Roemer (University of Basel; Swiss Institute of Bioinformatics) , Thomas P. Peacock (Imperial College London) , Neil G. Paterson (Diamond Light Source) , Mark A. Williams (Diamond Light Source) , David R. Hall (Diamond Light Source) , Elizabeth E. Fry (Wellcome Centre for Human Genetics, University of Oxford) , Juthathip Mongkolsapaya (Wellcome Centre for Human Genetics, University of Oxford; Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford) , Jingshan Ren (Wellcome Centre for Human Genetics, University of Oxford) , David I. Stuart (Wellcome Centre for Human Genetics, University of Oxford; Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford; Diamond Light Source) , Gavin R. Screaton (Wellcome Centre for Human Genetics, University of Oxford; Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Cell Reports

State: Published (Approved)
Published: March 2023
Diamond Proposal Number(s): 27009

Abstract: In November 2021 Omicron BA.1, containing a raft of new spike mutations emerged and quickly spread globally. Intense selection pressure to escape the antibody response produced by vaccines or SARS-CoV-2 infection then led to a rapid succession of Omicron sub-lineages with waves of BA.2 then BA.4/5 infection. Recently, many variants have emerged such as BQ.1 and XBB, which carry up to 8 additional RBD amino-acid substitutions compared to BA.2. We describe a panel of 25 potent mAbs generated from vaccinees suffering BA.2 breakthrough infections. Epitope mapping shows potent mAb binding shifting to 3 clusters, 2 corresponding to early-pandemic binding hotspots. The RBD mutations in recent variants map close to these binding sites and knock out or severely knock down neutralization activity of all but 1 potent mAb. This recent mAb escape corresponds with large falls in neutralization titre of vaccine or BA.1, BA.2 or BA.4/5 immune serum.

Diamond Keywords: COVID-19; Viruses

Subject Areas: Biology and Bio-materials


Instruments: I03-Macromolecular Crystallography , I04-Macromolecular Crystallography

Added On: 07/03/2023 10:05

Discipline Tags:

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

Technical Tags:

Diffraction Macromolecular Crystallography (MX)