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Horse immunization with short-chain consensus α-neurotoxin generates antibodies against broad spectrum of elapid venomous species.
Nat Commun. 2019 08 13; 10(1):3642.NC

Abstract

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.

Authors+Show Affiliations

Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnología, Universidad Nacional Autónoma de México - UNAM, Apartado Postal 510-3, Cuernavaca Morelos, 61500, Mexico. guillermo.delarosa.h@gmail.com. The Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, M5S3E1, Canada. guillermo.delarosa.h@gmail.com.Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnología, Universidad Nacional Autónoma de México - UNAM, Apartado Postal 510-3, Cuernavaca Morelos, 61500, Mexico.Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnología, Universidad Nacional Autónoma de México - UNAM, Apartado Postal 510-3, Cuernavaca Morelos, 61500, Mexico.Instituto Clodomiro Picado, Universidad de Costa Rica, San José, 11501, Costa Rica.Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnología, Universidad Nacional Autónoma de México - UNAM, Apartado Postal 510-3, Cuernavaca Morelos, 61500, Mexico.Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnología, Universidad Nacional Autónoma de México - UNAM, Apartado Postal 510-3, Cuernavaca Morelos, 61500, Mexico. corzo@ibt.unam.mx.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

31409779

Citation

de la Rosa, Guillermo, et al. "Horse Immunization With Short-chain Consensus Α-neurotoxin Generates Antibodies Against Broad Spectrum of Elapid Venomous Species." Nature Communications, vol. 10, no. 1, 2019, p. 3642.
de la Rosa G, Olvera F, Archundia IG, et al. Horse immunization with short-chain consensus α-neurotoxin generates antibodies against broad spectrum of elapid venomous species. Nat Commun. 2019;10(1):3642.
de la Rosa, G., Olvera, F., Archundia, I. G., Lomonte, B., Alagón, A., & Corzo, G. (2019). Horse immunization with short-chain consensus α-neurotoxin generates antibodies against broad spectrum of elapid venomous species. Nature Communications, 10(1), 3642. https://doi.org/10.1038/s41467-019-11639-2
de la Rosa G, et al. Horse Immunization With Short-chain Consensus Α-neurotoxin Generates Antibodies Against Broad Spectrum of Elapid Venomous Species. Nat Commun. 2019 08 13;10(1):3642. PubMed PMID: 31409779.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Horse immunization with short-chain consensus α-neurotoxin generates antibodies against broad spectrum of elapid venomous species. AU - de la Rosa,Guillermo, AU - Olvera,Felipe, AU - Archundia,Irving G, AU - Lomonte,Bruno, AU - Alagón,Alejandro, AU - Corzo,Gerardo, Y1 - 2019/08/13/ PY - 2018/11/26/received PY - 2019/07/23/accepted PY - 2019/8/15/entrez PY - 2019/8/15/pubmed PY - 2020/1/7/medline SP - 3642 EP - 3642 JF - Nature communications JO - Nat Commun VL - 10 IS - 1 N2 - 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. SN - 2041-1723 UR - https://www.unboundmedicine.com/medline/citation/31409779/Horse_immunization_with_short_chain_consensus_α_neurotoxin_generates_antibodies_against_broad_spectrum_of_elapid_venomous_species_ L2 - http://dx.doi.org/10.1038/s41467-019-11639-2 DB - PRIME DP - Unbound Medicine ER -