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

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 cont...

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Autores principales: Laustsen, Andreas H., Karatt-Vellatt, Aneesh, Masters, Edward W., Arias, Ana Silvia, Pus, Urska, Knudsen, Cecilie, Oscoz, Saioa, Slavny, Peter, Griffiths, Daniel T., Luther, Alice M., Leah, Rachael A., Lindholm, Majken, Lomonte, Bruno, Gutiérrez, José María, McCafferty, John
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6168529/
https://www.ncbi.nlm.nih.gov/pubmed/30279409
http://dx.doi.org/10.1038/s41467-018-06086-4
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author Laustsen, Andreas H.
Karatt-Vellatt, Aneesh
Masters, Edward W.
Arias, Ana Silvia
Pus, Urska
Knudsen, Cecilie
Oscoz, Saioa
Slavny, Peter
Griffiths, Daniel T.
Luther, Alice M.
Leah, Rachael A.
Lindholm, Majken
Lomonte, Bruno
Gutiérrez, José María
McCafferty, John
author_facet Laustsen, Andreas H.
Karatt-Vellatt, Aneesh
Masters, Edward W.
Arias, Ana Silvia
Pus, Urska
Knudsen, Cecilie
Oscoz, Saioa
Slavny, Peter
Griffiths, Daniel T.
Luther, Alice M.
Leah, Rachael A.
Lindholm, Majken
Lomonte, Bruno
Gutiérrez, José María
McCafferty, John
author_sort Laustsen, Andreas H.
collection PubMed
description 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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spelling pubmed-61685292018-10-04 In vivo neutralization of dendrotoxin-mediated neurotoxicity of black mamba venom by oligoclonal human IgG antibodies Laustsen, Andreas H. Karatt-Vellatt, Aneesh Masters, Edward W. Arias, Ana Silvia Pus, Urska Knudsen, Cecilie Oscoz, Saioa Slavny, Peter Griffiths, Daniel T. Luther, Alice M. Leah, Rachael A. Lindholm, Majken Lomonte, Bruno Gutiérrez, José María McCafferty, John Nat Commun Article 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. Nature Publishing Group UK 2018-10-02 /pmc/articles/PMC6168529/ /pubmed/30279409 http://dx.doi.org/10.1038/s41467-018-06086-4 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Laustsen, Andreas H.
Karatt-Vellatt, Aneesh
Masters, Edward W.
Arias, Ana Silvia
Pus, Urska
Knudsen, Cecilie
Oscoz, Saioa
Slavny, Peter
Griffiths, Daniel T.
Luther, Alice M.
Leah, Rachael A.
Lindholm, Majken
Lomonte, Bruno
Gutiérrez, José María
McCafferty, John
In vivo neutralization of dendrotoxin-mediated neurotoxicity of black mamba venom by oligoclonal human IgG antibodies
title In vivo neutralization of dendrotoxin-mediated neurotoxicity of black mamba venom by oligoclonal human IgG antibodies
title_full In vivo neutralization of dendrotoxin-mediated neurotoxicity of black mamba venom by oligoclonal human IgG antibodies
title_fullStr In vivo neutralization of dendrotoxin-mediated neurotoxicity of black mamba venom by oligoclonal human IgG antibodies
title_full_unstemmed In vivo neutralization of dendrotoxin-mediated neurotoxicity of black mamba venom by oligoclonal human IgG antibodies
title_short In vivo neutralization of dendrotoxin-mediated neurotoxicity of black mamba venom by oligoclonal human IgG antibodies
title_sort in vivo neutralization of dendrotoxin-mediated neurotoxicity of black mamba venom by oligoclonal human igg antibodies
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6168529/
https://www.ncbi.nlm.nih.gov/pubmed/30279409
http://dx.doi.org/10.1038/s41467-018-06086-4
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