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

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, John McCafferty, Bruno Lomonte, José M. Gutiérrez (), Andreas H. Laustsen () and Aneesh Karatt-Vellatt ()
Additional contact information
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.

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

Abstract: 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.

Date: 2023
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-36393-4

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DOI: 10.1038/s41467-023-36393-4

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