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Antibody-dependent enhancement of toxicity of myotoxin II from Bothrops asper

Author

Listed:
  • Christoffer V. Sørensen

    (Technical University of Denmark)

  • Julián Fernández

    (Universidad de Costa Rica)

  • Anna Christina Adams

    (Technical University of Denmark)

  • Helen H. K. Wildenauer

    (Technical University of Denmark)

  • Sanne Schoffelen

    (Technical University of Denmark)

  • Line Ledsgaard

    (Technical University of Denmark)

  • Manuela B. Pucca

    (Federal University of Roraima)

  • Michael Fiebig

    (Absolute Antibody Ltd, Wilton Centre, Redcar)

  • Felipe A. Cerni

    (University of the State of Amazonas)

  • Tulika Tulika

    (Technical University of Denmark)

  • Bjørn G. Voldborg

    (Technical University of Denmark)

  • Aneesh Karatt-Vellatt

    (IONTAS Ltd.)

  • J. Preben Morth

    (Technical University of Denmark)

  • Anne Ljungars

    (Technical University of Denmark)

  • Lise M. Grav

    (Technical University of Denmark)

  • Bruno Lomonte

    (Universidad de Costa Rica)

  • Andreas H. Laustsen

    (Technical University of Denmark)

Abstract

Improved therapies are needed against snakebite envenoming, which kills and permanently disables thousands of people each year. Recently developed neutralizing monoclonal antibodies against several snake toxins have shown promise in preclinical rodent models. Here, we use phage display technology to discover a human monoclonal antibody and show that this antibody causes antibody-dependent enhancement of toxicity (ADET) of myotoxin II from the venomous pit viper, Bothrops asper, in a mouse model of envenoming that mimics a snakebite. While clinical ADET related to snake venom has not yet been reported in humans, this report of ADET of a toxin from the animal kingdom highlights the necessity of assessing even well-known antibody formats in representative preclinical models to evaluate their therapeutic utility against toxins or venoms. This is essential to avoid potential deleterious effects as exemplified in the present study.

Suggested Citation

  • Christoffer V. Sørensen & Julián Fernández & Anna Christina Adams & Helen H. K. Wildenauer & Sanne Schoffelen & Line Ledsgaard & Manuela B. Pucca & Michael Fiebig & Felipe A. Cerni & Tulika Tulika & B, 2024. "Antibody-dependent enhancement of toxicity of myotoxin II from Bothrops asper," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-023-42624-5
    DOI: 10.1038/s41467-023-42624-5
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    References listed on IDEAS

    as
    1. Andreas H. Laustsen & Aneesh Karatt-Vellatt & Edward W. Masters & Ana Silvia Arias & Urska Pus & Cecilie Knudsen & Saioa Oscoz & Peter Slavny & Daniel T. Griffiths & Alice M. Luther & Rachael A. Leah , 2018. "In vivo neutralization of dendrotoxin-mediated neurotoxicity of black mamba venom by oligoclonal human IgG antibodies," Nature Communications, Nature, vol. 9(1), pages 1-9, December.
    2. Andreas H. Laustsen & Aneesh Karatt-Vellatt & Edward W. Masters & Ana Silvia Arias & Urska Pus & Cecilie Knudsen & Saioa Oscoz & Peter Slavny & Daniel T. Griffiths & Alice M. Luther & Rachael A. Leah , 2018. "Publisher Correction: In vivo neutralization of dendrotoxin-mediated neurotoxicity of black mamba venom by oligoclonal human IgG antibodies," Nature Communications, Nature, vol. 9(1), pages 1-1, December.
    3. Line Ledsgaard & Jack Wade & Timothy P. Jenkins & Kim Boddum & Irina Oganesyan & Julian A. Harrison & Pedro Villar & Rachael A. Leah & Renato Zenobi & Sanne Schoffelen & Bjørn Voldborg & Anne Ljungars, 2023. "Discovery and optimization of a broadly-neutralizing human monoclonal antibody against long-chain α-neurotoxins from snakes," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
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