Generation of SARS-CoV-2 escape mutations by monoclonal antibody therapy

Manon Ragonnet-Cronin; Rungtiwa Nutalai; Jiandong Huo; Aiste Dijokaite-Guraliuc; Raksha Das; Aekkachai Tuekprakhon; Piyada Supasa; Chang Liu; Muneeswaran Selvaraj; Natalie Groves; Hassan Hartman; Nicholas Ellaby; J. Mark Sutton; Mohammad W. Bahar; Daming Zhou; Elizabeth Fry; Jingshan Ren; Colin Brown; Paul Klenerman; Susanna J. Dunachie; Juthathip Mongkolsapaya; Susan Hopkins; Meera Chand; David I. Stuart; Gavin R. Screaton; Sakib Rokadiya

doi:10.1038/s41467-023-37826-w

Generation of SARS-CoV-2 escape mutations by monoclonal antibody therapy

Manon Ragonnet-Cronin^*, Rungtiwa Nutalai, Jiandong Huo^*, Aiste Dijokaite-Guraliuc, Raksha Das, Aekkachai Tuekprakhon, Piyada Supasa, Chang Liu, Muneeswaran Selvaraj, Natalie Groves, Hassan Hartman, Nicholas Ellaby, J. Mark Sutton, Mohammad W. Bahar, Daming Zhou, Elizabeth Fry, Jingshan Ren, Colin Brown, Paul Klenerman, Susanna J. DunachieJuthathip Mongkolsapaya, Susan Hopkins, Meera Chand, David I. Stuart^*, Gavin R. Screaton^*, Sakib Rokadiya^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

22 Citations (Scopus)

Abstract

COVID-19 patients at risk of severe disease may be treated with neutralising monoclonal antibodies (mAbs). To minimise virus escape from neutralisation these are administered as combinations e.g. casirivimab+imdevimab or, for antibodies targeting relatively conserved regions, individually e.g. sotrovimab. Unprecedented genomic surveillance of SARS-CoV-2 in the UK has enabled a genome-first approach to detect emerging drug resistance in Delta and Omicron cases treated with casirivimab+imdevimab and sotrovimab respectively. Mutations occur within the antibody epitopes and for casirivimab+imdevimab multiple mutations are present on contiguous raw reads, simultaneously affecting both components. Using surface plasmon resonance and pseudoviral neutralisation assays we demonstrate these mutations reduce or completely abrogate antibody affinity and neutralising activity, suggesting they are driven by immune evasion. In addition, we show that some mutations also reduce the neutralising activity of vaccine-induced serum.

Original language	English
Article number	3334
Journal	Nature Communications
Volume	14
Issue number	1
DOIs	https://doi.org/10.1038/s41467-023-37826-w
Publication status	Published - Dec 2023

Bibliographical note

Publisher Copyright:
© 2023, The Author(s).

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Ragonnet-Cronin, M., Nutalai, R., Huo, J., Dijokaite-Guraliuc, A., Das, R., Tuekprakhon, A., Supasa, P., Liu, C., Selvaraj, M., Groves, N., Hartman, H., Ellaby, N., Mark Sutton, J., Bahar, M. W., Zhou, D., Fry, E., Ren, J., Brown, C., Klenerman, P., ... Rokadiya, S. (2023). Generation of SARS-CoV-2 escape mutations by monoclonal antibody therapy. Nature Communications, 14(1), Article 3334. https://doi.org/10.1038/s41467-023-37826-w

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abstract = "COVID-19 patients at risk of severe disease may be treated with neutralising monoclonal antibodies (mAbs). To minimise virus escape from neutralisation these are administered as combinations e.g. casirivimab+imdevimab or, for antibodies targeting relatively conserved regions, individually e.g. sotrovimab. Unprecedented genomic surveillance of SARS-CoV-2 in the UK has enabled a genome-first approach to detect emerging drug resistance in Delta and Omicron cases treated with casirivimab+imdevimab and sotrovimab respectively. Mutations occur within the antibody epitopes and for casirivimab+imdevimab multiple mutations are present on contiguous raw reads, simultaneously affecting both components. Using surface plasmon resonance and pseudoviral neutralisation assays we demonstrate these mutations reduce or completely abrogate antibody affinity and neutralising activity, suggesting they are driven by immune evasion. In addition, we show that some mutations also reduce the neutralising activity of vaccine-induced serum.",

author = "Manon Ragonnet-Cronin and Rungtiwa Nutalai and Jiandong Huo and Aiste Dijokaite-Guraliuc and Raksha Das and Aekkachai Tuekprakhon and Piyada Supasa and Chang Liu and Muneeswaran Selvaraj and Natalie Groves and Hassan Hartman and Nicholas Ellaby and {Mark Sutton}, J. and Bahar, {Mohammad W.} and Daming Zhou and Elizabeth Fry and Jingshan Ren and Colin Brown and Paul Klenerman and Dunachie, {Susanna J.} and Juthathip Mongkolsapaya and Susan Hopkins and Meera Chand and Stuart, {David I.} and Screaton, {Gavin R.} and Sakib Rokadiya",

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Ragonnet-Cronin, M, Nutalai, R, Huo, J, Dijokaite-Guraliuc, A, Das, R, Tuekprakhon, A, Supasa, P, Liu, C, Selvaraj, M, Groves, N , Hartman, H, Ellaby, N, Mark Sutton, J, Bahar, MW, Zhou, D, Fry, E, Ren, J, Brown, C, Klenerman, P, Dunachie, SJ, Mongkolsapaya, J, Hopkins, S, Chand, M, Stuart, DI, Screaton, GR & Rokadiya, S 2023, 'Generation of SARS-CoV-2 escape mutations by monoclonal antibody therapy', Nature Communications, vol. 14, no. 1, 3334. https://doi.org/10.1038/s41467-023-37826-w

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AU - Ragonnet-Cronin, Manon

AU - Nutalai, Rungtiwa

AU - Huo, Jiandong

AU - Dijokaite-Guraliuc, Aiste

AU - Das, Raksha

AU - Tuekprakhon, Aekkachai

AU - Supasa, Piyada

AU - Liu, Chang

AU - Selvaraj, Muneeswaran

AU - Groves, Natalie

AU - Hartman, Hassan

AU - Ellaby, Nicholas

AU - Mark Sutton, J.

AU - Bahar, Mohammad W.

AU - Zhou, Daming

AU - Fry, Elizabeth

AU - Ren, Jingshan

AU - Brown, Colin

AU - Klenerman, Paul

AU - Dunachie, Susanna J.

AU - Mongkolsapaya, Juthathip

AU - Hopkins, Susan

AU - Chand, Meera

AU - Stuart, David I.

AU - Screaton, Gavin R.

AU - Rokadiya, Sakib

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VL - 14

JO - Nature Communications

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ER -

Generation of SARS-CoV-2 escape mutations by monoclonal antibody therapy

Abstract

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