Nature Communications (Apr 2024)

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

  • 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 Klenerman,
  • Susanna J. Dunachie,
  • Neil G. Paterson,
  • Mark A. Williams,
  • David R. Hall,
  • Elizabeth E. Fry,
  • Juthathip Mongkolsapaya,
  • Jingshan Ren,
  • David I. Stuart,
  • Gavin R. Screaton

DOI
https://doi.org/10.1038/s41467-024-47393-3
Journal volume & issue
Vol. 15, no. 1
pp. 1 – 10

Abstract

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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.