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Horse immunization with short-chain consensus α-neurotoxin generates antibodies against broad spectrum of elapid venomous species

Antivenoms are fundamental in the therapy for snakebites. In elapid venoms, there are toxins, e.g. short-chain α-neurotoxins, which are quite abundant, highly toxic, and consequently play a major role in envenomation processes. The core problem is that such α-neurotoxins are weakly immunogenic, and...

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Autores principales: de la Rosa, Guillermo, Olvera, Felipe, Archundia, Irving G., Lomonte, Bruno, Alagón, Alejandro, Corzo, Gerardo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6692343/
https://www.ncbi.nlm.nih.gov/pubmed/31409779
http://dx.doi.org/10.1038/s41467-019-11639-2
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author de la Rosa, Guillermo
Olvera, Felipe
Archundia, Irving G.
Lomonte, Bruno
Alagón, Alejandro
Corzo, Gerardo
author_facet de la Rosa, Guillermo
Olvera, Felipe
Archundia, Irving G.
Lomonte, Bruno
Alagón, Alejandro
Corzo, Gerardo
author_sort de la Rosa, Guillermo
collection PubMed
description Antivenoms are fundamental in the therapy for snakebites. In elapid venoms, there are toxins, e.g. short-chain α-neurotoxins, which are quite abundant, highly toxic, and consequently play a major role in envenomation processes. The core problem is that such α-neurotoxins are weakly immunogenic, and many current elapid antivenoms show low reactivity towards them. We have previously developed a recombinant consensus short-chain α-neurotoxin (ScNtx) based on sequences from the most lethal elapid venoms from America, Africa, Asia, and Oceania. Here we report that an antivenom generated by immunizing horses with ScNtx can successfully neutralize the lethality of pure recombinant and native short-chain α-neurotoxins, as well as whole neurotoxic elapid venoms from diverse genera such as Micrurus, Dendroaspis, Naja, Walterinnesia, Ophiophagus and Hydrophis. These results provide a proof-of-principle for using recombinant proteins with rationally designed consensus sequences as universal immunogens for developing next-generation antivenoms with higher effectiveness and broader neutralizing capacity.
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spelling pubmed-66923432019-08-15 Horse immunization with short-chain consensus α-neurotoxin generates antibodies against broad spectrum of elapid venomous species de la Rosa, Guillermo Olvera, Felipe Archundia, Irving G. Lomonte, Bruno Alagón, Alejandro Corzo, Gerardo Nat Commun Article Antivenoms are fundamental in the therapy for snakebites. In elapid venoms, there are toxins, e.g. short-chain α-neurotoxins, which are quite abundant, highly toxic, and consequently play a major role in envenomation processes. The core problem is that such α-neurotoxins are weakly immunogenic, and many current elapid antivenoms show low reactivity towards them. We have previously developed a recombinant consensus short-chain α-neurotoxin (ScNtx) based on sequences from the most lethal elapid venoms from America, Africa, Asia, and Oceania. Here we report that an antivenom generated by immunizing horses with ScNtx can successfully neutralize the lethality of pure recombinant and native short-chain α-neurotoxins, as well as whole neurotoxic elapid venoms from diverse genera such as Micrurus, Dendroaspis, Naja, Walterinnesia, Ophiophagus and Hydrophis. These results provide a proof-of-principle for using recombinant proteins with rationally designed consensus sequences as universal immunogens for developing next-generation antivenoms with higher effectiveness and broader neutralizing capacity. Nature Publishing Group UK 2019-08-13 /pmc/articles/PMC6692343/ /pubmed/31409779 http://dx.doi.org/10.1038/s41467-019-11639-2 Text en © The Author(s) 2019 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
de la Rosa, Guillermo
Olvera, Felipe
Archundia, Irving G.
Lomonte, Bruno
Alagón, Alejandro
Corzo, Gerardo
Horse immunization with short-chain consensus α-neurotoxin generates antibodies against broad spectrum of elapid venomous species
title Horse immunization with short-chain consensus α-neurotoxin generates antibodies against broad spectrum of elapid venomous species
title_full Horse immunization with short-chain consensus α-neurotoxin generates antibodies against broad spectrum of elapid venomous species
title_fullStr Horse immunization with short-chain consensus α-neurotoxin generates antibodies against broad spectrum of elapid venomous species
title_full_unstemmed Horse immunization with short-chain consensus α-neurotoxin generates antibodies against broad spectrum of elapid venomous species
title_short Horse immunization with short-chain consensus α-neurotoxin generates antibodies against broad spectrum of elapid venomous species
title_sort horse immunization with short-chain consensus α-neurotoxin generates antibodies against broad spectrum of elapid venomous species
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6692343/
https://www.ncbi.nlm.nih.gov/pubmed/31409779
http://dx.doi.org/10.1038/s41467-019-11639-2
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