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 () and Sakib Rokadiya ()
Additional contact information
Manon Ragonnet-Cronin: UK Health Security Agency
Rungtiwa Nutalai: University of Oxford
Jiandong Huo: University of Oxford, The Wellcome Centre for Human Genetics
Aiste Dijokaite-Guraliuc: University of Oxford
Raksha Das: University of Oxford
Aekkachai Tuekprakhon: University of Oxford
Piyada Supasa: University of Oxford
Chang Liu: University of Oxford
Muneeswaran Selvaraj: University of Oxford
Natalie Groves: UK Health Security Agency
Hassan Hartman: UK Health Security Agency
Nicholas Ellaby: UK Health Security Agency
J. Mark Sutton: UK Health Security Agency
Mohammad W. Bahar: University of Oxford, The Wellcome Centre for Human Genetics
Daming Zhou: University of Oxford, The Wellcome Centre for Human Genetics
Elizabeth Fry: University of Oxford, The Wellcome Centre for Human Genetics
Jingshan Ren: University of Oxford, The Wellcome Centre for Human Genetics
Colin Brown: UK Health Security Agency
Paul Klenerman: University of Oxford
Susanna J. Dunachie: University of Oxford
Juthathip Mongkolsapaya: University of Oxford
Susan Hopkins: UK Health Security Agency
Meera Chand: UK Health Security Agency
David I. Stuart: University of Oxford, The Wellcome Centre for Human Genetics
Gavin R. Screaton: University of Oxford
Sakib Rokadiya: UK Health Security Agency

Nature Communications, 2023, vol. 14, issue 1, 1-12

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-37826-w

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