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In vivo neutralization of dendrotoxin-mediated neurotoxicity of black mamba venom by oligoclonal human IgG antibodies

Author

Listed:
  • Andreas H. Laustsen

    (Technical University of Denmark)

  • Aneesh Karatt-Vellatt

    (IONTAS Ltd.)

  • Edward W. Masters

    (IONTAS Ltd.)

  • Ana Silvia Arias

    (Universidad de Costa Rica)

  • Urska Pus

    (Technical University of Denmark)

  • Cecilie Knudsen

    (Technical University of Denmark)

  • Saioa Oscoz

    (Universidad de Costa Rica)

  • Peter Slavny

    (IONTAS Ltd.)

  • Daniel T. Griffiths

    (IONTAS Ltd.)

  • Alice M. Luther

    (IONTAS Ltd.)

  • Rachael A. Leah

    (IONTAS Ltd.)

  • Majken Lindholm

    (IONTAS Ltd.)

  • Bruno Lomonte

    (Universidad de Costa Rica)

  • José María Gutiérrez

    (Universidad de Costa Rica)

  • John McCafferty

    (IONTAS Ltd.)

Abstract

The black mamba (Dendroaspis polylepis) is one of the most feared snake species of the African savanna. It has a potent, fast-acting neurotoxic venom comprised of dendrotoxins and α-neurotoxins associated with high fatality in untreated victims. Current antivenoms are both scarce on the African continent and present a number of drawbacks as they are derived from the plasma of hyper-immunized large mammals. Here, we describe the development of an experimental recombinant antivenom by a combined toxicovenomics and phage display approach. The recombinant antivenom is based on a cocktail of fully human immunoglobulin G (IgG) monoclonal antibodies capable of neutralizing dendrotoxin-mediated neurotoxicity of black mamba whole venom in a rodent model. Our results show the potential use of fully human monoclonal IgGs against animal toxins and the first use of oligoclonal human IgG mixtures against experimental snakebite envenoming.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-06086-4
    DOI: 10.1038/s41467-018-06086-4
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    Cited by:

    1. 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.
    2. Melisa Benard-Valle & Yessica Wouters & Anne Ljungars & Giang Thi Tuyet Nguyen & Shirin Ahmadi & Tasja Wainani Ebersole & Camilla Holst Dahl & Alid Guadarrama-Martínez & Frederikke Jeppesen & Helena E, 2024. "In vivo neutralization of coral snake venoms with an oligoclonal nanobody mixture in a murine challenge model," Nature Communications, Nature, vol. 15(1), pages 1-13, 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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