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:10.1038/s41467-024-47393-3

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

Nat Commun. 2024 Apr 16;15(1):3284. doi: 10.1038/s41467-024-47393-3.

Authors

Chang Liu^#^{1

2}, Raksha Das^#², Aiste Dijokaite-Guraliuc^#², Daming Zhou^#^{1

3

4}, Alexander J Mentzer^{2

5}, Piyada Supasa², Muneeswaran Selvaraj², Helen M E Duyvesteyn³, Thomas G Ritter⁵, Nigel Temperton⁶, Paul Klenerman^{5

7

8

9}, Susanna J Dunachie^{5

7

10

11}, Neil G Paterson¹², Mark A Williams¹², David R Hall¹², Elizabeth E Fry¹³, Juthathip Mongkolsapaya^{14

15

16}, Jingshan Ren¹⁷, David I Stuart^{18

19

20}, Gavin R Screaton^{21

22}

Affiliations

¹ Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford, Oxford, UK.
² Nuffield Department of Medicine, Centre for Human Genetics, University of Oxford, Oxford, UK.
³ Division of Structural Biology, Nuffield Department of Medicine, University of Oxford, The Wellcome Centre for Human Genetics, Oxford, UK.
⁴ College of Life Sciences, Zhejiang University, Hangzhou, 310058, China.
⁵ Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
⁶ Viral Pseudotype Unit, Medway School of Pharmacy, University of Kent and Greenwich Chatham Maritime, Kent, ME4 4TB, UK.
⁷ Peter Medawar Building for Pathogen Research, Oxford, UK.
⁸ Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.
⁹ NIHR Oxford Biomedical Research Centre, Oxford, UK.
¹⁰ Nuffield Department of Medicine, Centre for Tropical Medicine and Global Health, University of Oxford, Oxford, UK.
¹¹ Mahidol-Oxford Tropical Medicine Research Unit, Bangkok, Thailand.
¹² Diamond Light Source Ltd, Harwell Science & Innovation Campus, Didcot, UK.
¹³ Division of Structural Biology, Nuffield Department of Medicine, University of Oxford, The Wellcome Centre for Human Genetics, Oxford, UK. [email protected].
¹⁴ Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford, Oxford, UK. [email protected].
¹⁵ Nuffield Department of Medicine, Centre for Human Genetics, University of Oxford, Oxford, UK. [email protected].
¹⁶ Mahidol-Oxford Tropical Medicine Research Unit, Bangkok, Thailand. [email protected].
¹⁷ Division of Structural Biology, Nuffield Department of Medicine, University of Oxford, The Wellcome Centre for Human Genetics, Oxford, UK. [email protected].
¹⁸ Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford, Oxford, UK. [email protected].
¹⁹ Division of Structural Biology, Nuffield Department of Medicine, University of Oxford, The Wellcome Centre for Human Genetics, Oxford, UK. [email protected].
²⁰ Diamond Light Source Ltd, Harwell Science & Innovation Campus, Didcot, UK. [email protected].
²¹ Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford, Oxford, UK. [email protected].
²² Nuffield Department of Medicine, Centre for Human Genetics, University of Oxford, Oxford, UK. [email protected].

^# Contributed equally.

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.

MeSH terms

Antibodies, Monoclonal*
Antibodies, Neutralizing
Antibodies, Viral
Humans
Mutation
Postoperative Complications*
SARS-CoV-2 / genetics

Substances

Antibodies, Monoclonal
Antibodies, Neutralizing
Antibodies, Viral

Abstract

MeSH terms

Substances

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