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

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

University of Oxford
University of Oxford
College of Life Sciences, Zhejiang University
Oxford University Hospitals NHS Foundation Trust
Medway School of Pharmacy
University of Oxford Medical Sciences Division
NIHR Oxford Biomedical Research Centre
Mahidol University
Diamond Light Source

Research output: Contribution to a Journal (Peer & Non Peer) › Article › peer-review

15 Citations (Scopus)

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.

Original language	English
Article number	3284
Journal	Nature Communications
Volume	15
Issue number	1
DOIs	https://doi.org/10.1038/s41467-024-47393-3
Publication status	Published - Dec 2024
Externally published	Yes

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This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

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Liu, C., Das, R., Dijokaite-Guraliuc, A., Zhou, D., Mentzer, A. J., Supasa, P., Selvaraj, M., Duyvesteyn, H. M. E., Ritter, T. G., Temperton, N., Klenerman, P., Dunachie, S. J., Paterson, N. G., Williams, M. A., Hall, D. R., Fry, E. E., Mongkolsapaya, J., Ren, J., Stuart, D. I., & Screaton, G. R. (2024). Emerging variants develop total escape from potent monoclonal antibodies induced by BA.4/5 infection. Nature Communications, 15(1), Article 3284. https://doi.org/10.1038/s41467-024-47393-3

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

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 {\textquoteleft}FLip{\textquoteright} mutations at positions 455 and 456. Interestingly, activity of some mAbs is regained on the recently reported variant BA.2.86.",

author = "Chang Liu and Raksha Das and Aiste Dijokaite-Guraliuc and Daming Zhou and Mentzer, \{Alexander J.\} and Piyada Supasa and Muneeswaran Selvaraj and Duyvesteyn, \{Helen M.E.\} and Ritter, \{Thomas G.\} and Nigel Temperton and Paul Klenerman and Dunachie, \{Susanna J.\} and Paterson, \{Neil G.\} and Williams, \{Mark A.\} and Hall, \{David R.\} and Fry, \{Elizabeth E.\} and Juthathip Mongkolsapaya and Jingshan Ren and Stuart, \{David I.\} and Screaton, \{Gavin R.\}",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2024.",

year = "2024",

month = dec,

doi = "10.1038/s41467-024-47393-3",

language = "English",

volume = "15",

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Liu, C, Das, R, Dijokaite-Guraliuc, A, Zhou, D, Mentzer, AJ, Supasa, P, Selvaraj, M, Duyvesteyn, HME, Ritter, TG, Temperton, N, Klenerman, P, Dunachie, SJ, Paterson, NG, Williams, MA, Hall, DR, Fry, EE, Mongkolsapaya, J, Ren, J, Stuart, DI & Screaton, GR 2024, 'Emerging variants develop total escape from potent monoclonal antibodies induced by BA.4/5 infection', Nature Communications, vol. 15, no. 1, 3284. https://doi.org/10.1038/s41467-024-47393-3

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AU - Liu, Chang

AU - Das, Raksha

AU - Dijokaite-Guraliuc, Aiste

AU - Zhou, Daming

AU - Mentzer, Alexander J.

AU - Supasa, Piyada

AU - Selvaraj, Muneeswaran

AU - Duyvesteyn, Helen M.E.

AU - Ritter, Thomas G.

AU - Temperton, Nigel

AU - Klenerman, Paul

AU - Dunachie, Susanna J.

AU - Paterson, Neil G.

AU - Williams, Mark A.

AU - Hall, David R.

AU - Fry, Elizabeth E.

AU - Mongkolsapaya, Juthathip

AU - Ren, Jingshan

AU - Stuart, David I.

AU - Screaton, Gavin R.

PY - 2024/12

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N2 - 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.

AB - 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.

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SN - 2041-1723

VL - 15

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 3284

ER -

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

Abstract

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