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Discovery and optimization of a broadly-neutralizing human monoclonal antibody against long-chain α-neurotoxins from snakes

Author

Listed:
  • Line Ledsgaard

    (Technical University of Denmark)

  • Jack Wade

    (Technical University of Denmark)

  • Timothy P. Jenkins

    (Technical University of Denmark)

  • Kim Boddum

    (Sophion Bioscience)

  • Irina Oganesyan

    (Department of Chemistry and Applied Biosciences, ETH Zurich)

  • Julian A. Harrison

    (Department of Chemistry and Applied Biosciences, ETH Zurich)

  • Pedro Villar

    (IONTAS Ltd.)

  • Rachael A. Leah

    (IONTAS Ltd.)

  • Renato Zenobi

    (Department of Chemistry and Applied Biosciences, ETH Zurich)

  • Sanne Schoffelen

    (Technical University of Denmark)

  • Bjørn Voldborg

    (Technical University of Denmark)

  • Anne Ljungars

    (Technical University of Denmark)

  • John McCafferty

    (IONTAS Ltd.)

  • Bruno Lomonte

    (Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica)

  • José M. Gutiérrez

    (Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica)

  • Andreas H. Laustsen

    (Technical University of Denmark)

  • Aneesh Karatt-Vellatt

    (IONTAS Ltd.)

Abstract

Snakebite envenoming continues to claim many lives across the globe, necessitating the development of improved therapies. To this end, broadly-neutralizing human monoclonal antibodies may possess advantages over current plasma-derived antivenoms by offering superior safety and high neutralization capacity. Here, we report the establishment of a pipeline based on phage display technology for the discovery and optimization of high affinity broadly-neutralizing human monoclonal antibodies. This approach yielded a recombinant human antibody with superior broadly-neutralizing capacities in vitro and in vivo against different long-chain α-neurotoxins from elapid snakes. This antibody prevents lethality induced by Naja kaouthia whole venom at an unprecedented low molar ratio of one antibody per toxin and prolongs the survival of mice injected with Dendroaspis polylepis or Ophiophagus hannah whole venoms.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-36393-4
    DOI: 10.1038/s41467-023-36393-4
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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.
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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.

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    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.
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