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

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, Majken Lindholm, Bruno Lomonte, José María Gutiérrez () and John McCafferty
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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.

Nature Communications, 2018, vol. 9, issue 1, 1-9

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-06086-4

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