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

Andreas H. Laustsen(Technical University of Denmark), Aneesh Karatt-Vellatt(Agricultural Development Advisory Service (United Kingdom)), Edward W. Masters, Ana Silvia Arias(Universidad de Costa Rica), Urška Puš(Technical University of Denmark), Cecilie Knudsen(Technical University of Denmark), Saioa Oscoz(Universidad de Costa Rica), Peter Slavny, Daniel T. Griffiths, Alice M. Luther, Rachael A. Leah, Majken Lindholm, Bruno Lomonte(Universidad de Costa Rica), José Marı́a Gutiérrez(Universidad de Costa Rica), John McCafferty
Nature Communications
September 20, 2018
Cited by 124Open Access
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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.


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