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Generation of SARS-CoV-2 escape mutations by monoclonal antibody therapy.
Ragonnet-Cronin, Manon; Nutalai, Rungtiwa; Huo, Jiandong; Dijokaite-Guraliuc, Aiste; Das, Raksha; Tuekprakhon, Aekkachai; Supasa, Piyada; Liu, Chang; Selvaraj, Muneeswaran; Groves, Natalie; Hartman, Hassan; Ellaby, Nicholas; Mark Sutton, J; Bahar, Mohammad W; Zhou, Daming; Fry, Elizabeth; Ren, Jingshan; Brown, Colin; Klenerman, Paul; Dunachie, Susanna J; Mongkolsapaya, Juthathip; Hopkins, Susan; Chand, Meera; Stuart, David I; Screaton, Gavin R; Rokadiya, Sakib.
  • Ragonnet-Cronin M; Genomics Public Health Analysis, UK Health Security Agency, London, UK. manonragonnet@uchicago.edu.
  • Nutalai R; Centre for Global Infectious Disease Analysis, Imperial College London, London, England. manonragonnet@uchicago.edu.
  • Huo J; Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Dijokaite-Guraliuc A; Division of Structural Biology, Nuffield Department of Medicine, University of Oxford, The Wellcome Centre for Human Genetics, Oxford, UK. dongdong.imm.ox.ac.uk@gmail.com.
  • Das R; Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Tuekprakhon A; Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Supasa P; Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Liu C; Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Selvaraj M; Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Groves N; Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford, Oxford, UK.
  • Hartman H; Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Ellaby N; Genomics Public Health Analysis, UK Health Security Agency, London, UK.
  • Mark Sutton J; Genomics Public Health Analysis, UK Health Security Agency, London, UK.
  • Bahar MW; Genomics Public Health Analysis, UK Health Security Agency, London, UK.
  • Zhou D; Genomics Public Health Analysis, UK Health Security Agency, London, UK.
  • Fry E; Division of Structural Biology, Nuffield Department of Medicine, University of Oxford, The Wellcome Centre for Human Genetics, Oxford, UK.
  • Ren J; Division of Structural Biology, Nuffield Department of Medicine, University of Oxford, The Wellcome Centre for Human Genetics, Oxford, UK.
  • Brown C; Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford, Oxford, UK.
  • Klenerman P; Division of Structural Biology, Nuffield Department of Medicine, University of Oxford, The Wellcome Centre for Human Genetics, Oxford, UK.
  • Dunachie SJ; Division of Structural Biology, Nuffield Department of Medicine, University of Oxford, The Wellcome Centre for Human Genetics, Oxford, UK.
  • Mongkolsapaya J; Genomics Public Health Analysis, UK Health Security Agency, London, UK.
  • Hopkins S; Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Chand M; Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
  • Stuart DI; Translational Gastroenterology Unit, University of Oxford, Oxford, UK.
  • Screaton GR; NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, UK.
  • Rokadiya S; Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Nat Commun ; 14(1): 3334, 2023 06 07.
Article in English | MEDLINE | ID: covidwho-20241659
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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: SARS-CoV-2 / COVID-19 Type of study: Prognostic study Topics: Vaccines / Variants Limits: Humans Language: English Journal: Nat Commun Journal subject: Biology / Science Year: 2023 Document Type: Article Affiliation country: S41467-023-37826-w

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Full text: Available Collection: International databases Database: MEDLINE Main subject: SARS-CoV-2 / COVID-19 Type of study: Prognostic study Topics: Vaccines / Variants Limits: Humans Language: English Journal: Nat Commun Journal subject: Biology / Science Year: 2023 Document Type: Article Affiliation country: S41467-023-37826-w