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Emerging variants develop total escape from potent monoclonal antibodies induced by BA.4/5 infection

Author

Listed:
  • Chang Liu

    (University of Oxford
    University of Oxford)

  • Raksha Das

    (University of Oxford)

  • Aiste Dijokaite-Guraliuc

    (University of Oxford)

  • Daming Zhou

    (University of Oxford
    The Wellcome Centre for Human Genetics
    Zhejiang University)

  • Alexander J. Mentzer

    (University of Oxford
    Oxford University Hospitals NHS Foundation Trust)

  • Piyada Supasa

    (University of Oxford)

  • Muneeswaran Selvaraj

    (University of Oxford)

  • Helen M. E. Duyvesteyn

    (The Wellcome Centre for Human Genetics)

  • 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
    University of Oxford
    NIHR Oxford Biomedical Research Centre)

  • Susanna J. Dunachie

    (Oxford University Hospitals NHS Foundation Trust
    Peter Medawar Building for Pathogen Research
    University of Oxford
    Mahidol-Oxford Tropical Medicine Research Unit)

  • Neil G. Paterson

    (Harwell Science & Innovation Campus)

  • Mark A. Williams

    (Harwell Science & Innovation Campus)

  • David R. Hall

    (Harwell Science & Innovation Campus)

  • Elizabeth E. Fry

    (The Wellcome Centre for Human Genetics)

  • Juthathip Mongkolsapaya

    (University of Oxford
    University of Oxford
    Mahidol-Oxford Tropical Medicine Research Unit)

  • Jingshan Ren

    (The Wellcome Centre for Human Genetics)

  • David I. Stuart

    (University of Oxford
    The Wellcome Centre for Human Genetics
    Harwell Science & Innovation Campus)

  • Gavin R. Screaton

    (University of Oxford
    University of Oxford)

Abstract

The rapid evolution of SARS-CoV-2 is driven in part by a need to evade the antibody response in the face of high levels of immunity. Here, we isolate spike (S) binding monoclonal antibodies (mAbs) from vaccinees who suffered vaccine break-through infections with Omicron sub lineages BA.4 or BA.5. Twenty eight potent antibodies are isolated and characterised functionally, and in some cases structurally. Since the emergence of BA.4/5, SARS-CoV-2 has continued to accrue mutations in the S protein, to understand this we characterize neutralization of a large panel of variants and demonstrate a steady attrition of neutralization by the panel of BA.4/5 mAbs culminating in total loss of function with recent XBB.1.5.70 variants containing the so-called ‘FLip’ mutations at positions 455 and 456. Interestingly, activity of some mAbs is regained on the recently reported variant BA.2.86.

Suggested Citation

  • Chang Liu & Raksha Das & Aiste Dijokaite-Guraliuc & Daming Zhou & Alexander J. Mentzer & Piyada Supasa & Muneeswaran Selvaraj & Helen M. E. Duyvesteyn & Thomas G. Ritter & Nigel Temperton & Paul Klene, 2024. "Emerging variants develop total escape from potent monoclonal antibodies induced by BA.4/5 infection," Nature Communications, Nature, vol. 15(1), pages 1-10, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-47393-3
    DOI: 10.1038/s41467-024-47393-3
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