Cell Reports (Apr 2023)
Rapid escape of new SARS-CoV-2 Omicron variants from BA.2-directed antibody responses
- Aiste Dijokaite-Guraliuc,
- Raksha Das,
- Daming Zhou,
- Helen M. Ginn,
- Chang Liu,
- Helen M.E. Duyvesteyn,
- Jiandong Huo,
- Rungtiwa Nutalai,
- Piyada Supasa,
- Muneeswaran Selvaraj,
- Thushan I. de Silva,
- Megan Plowright,
- Thomas A.H. Newman,
- Hailey Hornsby,
- Alexander J. Mentzer,
- Donal Skelly,
- Thomas G. Ritter,
- Nigel Temperton,
- Paul Klenerman,
- Eleanor Barnes,
- Susanna J. Dunachie,
- Cornelius Roemer,
- Thomas P. Peacock,
- Neil G. Paterson,
- Mark A. Williams,
- David R. Hall,
- Elizabeth E. Fry,
- Juthathip Mongkolsapaya,
- Jingshan Ren,
- David I. Stuart,
- Gavin R. Screaton,
- Christopher Conlon,
- Alexandra Deeks,
- John Frater,
- Siobhan Gardiner,
- Anni Jämsén,
- Katie Jeffery,
- Tom Malone,
- Eloise Phillips,
- Barbara Kronsteiner-Dobramysl,
- Priyanka Abraham,
- Sagida Bibi,
- Teresa Lambe,
- Stephanie Longet,
- Tom Tipton,
- Miles Carrol,
- Lizzie Stafford
Affiliations
- Aiste Dijokaite-Guraliuc
- Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK
- Raksha Das
- Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK
- Daming Zhou
- Division of Structural Biology, Nuffield Department of Medicine, University of Oxford, The Wellcome Centre for Human Genetics, Oxford, UK; Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford, Oxford, UK
- Helen M. Ginn
- Diamond Light Source, Ltd., Harwell Science & Innovation Campus, Didcot, UK
- Chang Liu
- Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK; Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford, Oxford, UK
- Helen M.E. Duyvesteyn
- Division of Structural Biology, Nuffield Department of Medicine, University of Oxford, The Wellcome Centre for Human Genetics, Oxford, UK
- Jiandong Huo
- Division of Structural Biology, Nuffield Department of Medicine, University of Oxford, The Wellcome Centre for Human Genetics, Oxford, UK
- Rungtiwa Nutalai
- Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK
- Piyada Supasa
- Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK
- Muneeswaran Selvaraj
- Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK
- Thushan I. de Silva
- Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK; Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
- Megan Plowright
- Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK; Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
- Thomas A.H. Newman
- Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK; Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
- Hailey Hornsby
- Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK
- Alexander J. Mentzer
- Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK; Oxford University Hospitals NHS Foundation Trust, Oxford, UK
- Donal Skelly
- Oxford University Hospitals NHS Foundation Trust, Oxford, UK; Peter Medawar Building for Pathogen Research, Oxford, UK; Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK
- Thomas G. Ritter
- Oxford University Hospitals NHS Foundation Trust, Oxford, UK
- Nigel Temperton
- Viral Pseudotype Unit, Medway School of Pharmacy, University of Kent and Greenwich Chatham Maritime, Kent, UK
- Paul Klenerman
- Oxford University Hospitals NHS Foundation Trust, Oxford, UK; Peter Medawar Building for Pathogen Research, Oxford, UK; NIHR Oxford Biomedical Research Centre, Oxford, UK; Translational Gastroenterology Unit, University of Oxford, Oxford, UK
- Eleanor Barnes
- Oxford University Hospitals NHS Foundation Trust, Oxford, UK; Peter Medawar Building for Pathogen Research, Oxford, UK; NIHR Oxford Biomedical Research Centre, Oxford, UK; Translational Gastroenterology Unit, University of Oxford, Oxford, UK
- Susanna J. Dunachie
- Oxford University Hospitals NHS Foundation Trust, Oxford, UK; Peter Medawar Building for Pathogen Research, Oxford, UK; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK; Mahidol-Oxford Tropical Medicine Research Unit, Bangkok, Thailand; Department of Medicine, University of Oxford, Oxford, UK
- Cornelius Roemer
- Biozentrum, University of Basel, Basel, Switzerland; Swiss Institute of Bioinformatics, Basel, Switzerland
- Thomas P. Peacock
- Department of Infectious Disease, Imperial College London, London, UK
- Neil G. Paterson
- Diamond Light Source, Ltd., Harwell Science & Innovation Campus, Didcot, UK
- Mark A. Williams
- Diamond Light Source, Ltd., Harwell Science & Innovation Campus, Didcot, UK
- David R. Hall
- Diamond Light Source, Ltd., Harwell Science & Innovation Campus, Didcot, UK
- Elizabeth E. Fry
- Division of Structural Biology, Nuffield Department of Medicine, University of Oxford, The Wellcome Centre for Human Genetics, Oxford, UK; Corresponding author
- Juthathip Mongkolsapaya
- Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK; Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford, Oxford, UK; Corresponding author
- Jingshan Ren
- Division of Structural Biology, Nuffield Department of Medicine, University of Oxford, The Wellcome Centre for Human Genetics, Oxford, UK; Corresponding author
- David I. Stuart
- Division of Structural Biology, Nuffield Department of Medicine, University of Oxford, The Wellcome Centre for Human Genetics, Oxford, UK; Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford, Oxford, UK; Diamond Light Source, Ltd., Harwell Science & Innovation Campus, Didcot, UK; Corresponding author
- Gavin R. Screaton
- Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK; Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford, Oxford, UK; Corresponding author
- Christopher Conlon
- Alexandra Deeks
- John Frater
- Siobhan Gardiner
- Anni Jämsén
- Katie Jeffery
- Tom Malone
- Eloise Phillips
- Barbara Kronsteiner-Dobramysl
- Priyanka Abraham
- Sagida Bibi
- Teresa Lambe
- Stephanie Longet
- Tom Tipton
- Miles Carrol
- Lizzie Stafford
- Journal volume & issue
-
Vol. 42,
no. 4
p. 112271
Abstract
Summary: 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 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection then led to a rapid succession of Omicron sub-lineages with waves of BA.2 and then BA.4/5 infection. Recently, many variants have emerged such as BQ.1 and XBB, which carry up to 8 additional receptor-binding domain (RBD) amino acid substitutions compared with BA.2. We describe a panel of 25 potent monoclonal antibodies (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 titer of vaccine or BA.1, BA.2, or BA.4/5 immune serum.
