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 & Aneesh Karatt-Vellatt



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.

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