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Home / Equine Research Bank / Nat Commun / Horse immunization with short-chain consensus α-neurot...
Nature communications2019; 10(1); 3642; doi: 10.1038/s41467-019-11639-2

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

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.
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Publication Date: 2019-08-13 PubMed ID: 31409779PubMed Central: PMC6692343DOI: 10.1038/s41467-019-11639-2Google Scholar: Lookup
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  • Non-U.S. Gov't

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This study presents a promising breakthrough in the development of antivenoms for treatment against snakebites. The researchers discovered that antibodies produced by horses immunized with a specially redesigned neurotoxin could shield against toxins from a wide range of venomous snake species.

Introduction

  • The research focuses on improving the effectiveness of antivenoms used to treat venomous snakebites, with particular emphasis on elapid venoms which contain highly toxic short-chain α-neurotoxins. These toxins are abundant in such venoms and play a critical role in the envenomation process.
  • The challenge, however, is that these α-neurotoxins are weakly immunogenic, meaning they do not provoke a strong immune response. As a result, many of the current antivenoms used against elapid venom show lower efficacy.

Development of the Consensus Short-Chain α-Neurotoxin (ScNtx)

  • To overcome this problem, the team of researchers devised a redesigned, consensus short-chain α-neurotoxin (ScNtx). This sequence was based on the most lethal elapid venoms from various regions around the world including America, Africa, Asia, and Oceania.
  • The synthetic ScNtx was intended to act as a universal toxin stimulant to generate a more effective immune response against multiple venoms.

Immunization and Resulting Antivenom

  • The researchers then immunized horses with this ScNtx, which led to the production of antibodies capable of neutralizing a variety of neurotoxins.
  • These horse-produced antibodies, it was found, could effectively neutralize the lethality of pure recombinant and native short-chain α-neurotoxins, as well as the venom from several snake species including Micrurus, Dendroaspis, Naja, Walterinnesia, Ophiophagus, and Hydrophis.

Conclusion and Future Implications

  • The study concludes by identifying this approach as a proof-of-concept, demonstrating the potential of using rationally designed recombinant proteins as universal immunogens. Such a method could pave the way for the development of a new generation of antivenoms with improved potency and broader neutralizing capacity.
  • Such next-generation antivenoms could greatly improve the treatment of venomous snakebites, potentially providing a universal treatment for many different types of venoms.

Cite This Article

APA
de la Rosa G, Olvera F, Archundia IG, Lomonte B, Alagón A, Corzo G. (2019). Horse immunization with short-chain consensus α-neurotoxin generates antibodies against broad spectrum of elapid venomous species. Nat Commun, 10(1), 3642. https://doi.org/10.1038/s41467-019-11639-2

Publication

Nature communications
ISSN: 2041-1723
NlmUniqueID: 101528555
Country: England
Language: English
Volume: 10
Issue: 1
Pages: 3642
PII: 3642

Researcher Affiliations

de la Rosa, Guillermo
  • 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.
Olvera, Felipe
  • Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnología, Universidad Nacional Autónoma de México - UNAM, Apartado Postal 510-3, Cuernavaca Morelos, 61500, Mexico.
Archundia, Irving G
  • Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnología, Universidad Nacional Autónoma de México - UNAM, Apartado Postal 510-3, Cuernavaca Morelos, 61500, Mexico.
Lomonte, Bruno
  • Instituto Clodomiro Picado, Universidad de Costa Rica, San José, 11501, Costa Rica.
Alagón, Alejandro
  • Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnología, Universidad Nacional Autónoma de México - UNAM, Apartado Postal 510-3, Cuernavaca Morelos, 61500, Mexico.
Corzo, Gerardo
  • 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.

MeSH Terms

  • Amino Acid Sequence
  • Animals
  • Antibodies / immunology
  • Elapid Venoms / genetics
  • Elapid Venoms / immunology
  • Elapidae / genetics
  • Elapidae / immunology
  • Horses
  • Immunization
  • Male
  • Mice
  • Neurotoxins / chemistry
  • Neurotoxins / genetics
  • Neurotoxins / immunology
  • Sequence Alignment

Conflict of Interest Statement

The authors declare no competing interests.

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