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PLoS neglected tropical diseases2024; 18(5); e0012187; doi: 10.1371/journal.pntd.0012187

Comparison of the intrageneric neutralization scope of monospecific, bispecific/monogeneric and polyspecific/monogeneric antisera raised in horses immunized with sub-Saharan African snake venoms.

Abstract: Snakebite envenomation inflicts a high burden of mortality and morbidity in sub-Saharan Africa. Antivenoms are the mainstay in the therapy of envenomation, and there is an urgent need to develop antivenoms of broad neutralizing efficacy for this region. The venoms used as immunogens to manufacture snake antivenoms are normally selected considering their medical importance and availability. Additionally, their ability to induce antibody responses with high neutralizing capability should be considered, an issue that involves the immunization scheme and the animal species being immunized. Results: Using the lethality neutralization assay in mice, we compared the intrageneric neutralization scope of antisera generated by immunization of horses with monospecific, bispecific/monogeneric, and polyspecific/monogeneric immunogens formulated with venoms of Bitis spp., Echis spp., Dendroaspis spp., spitting Naja spp. or non-spitting Naja spp. It was found that the antisera raised by all the immunogens were able to neutralize the homologous venoms and, with a single exception, the heterologous congeneric venoms (considering spitting and non-spitting Naja separately). In general, the polyspecific antisera of Bitis spp, Echis spp, and Dendroaspis spp gave the best neutralization profile against venoms of these genera. For spitting Naja venoms, there were no significant differences in the neutralizing ability between monospecific, bispecific and polyspecific antisera. A similar result was obtained in the case of non-spitting Naja venoms, except that polyspecific antiserum was more effective against the venoms of N. melanoleuca and N. nivea as compared to the monospecific antiserum. Conclusions: The use of polyspecific immunogens is the best alternative to produce monogeneric antivenoms with wide neutralizing coverage against venoms of sub-Saharan African snakes of the Bitis, Echis, Naja (non-spitting) and Dendroaspis genera. On the other hand, a monospecific immunogen composed of venom of Naja nigricollis is suitable to produce a monogeneric antivenom with wide neutralizing coverage against venoms of spitting Naja spp. These findings can be used in the design of antivenoms of wide neutralizing scope for sub-Saharan Africa.
Copyright: © 2024 Sánchez et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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Publication Date: 2024-05-29 PubMed ID: 38809847PubMed Central: PMC11135691DOI: 10.1371/journal.pntd.0012187Google Scholar: Lookup
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  • Journal Article
  • Comparative Study

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.

Objective Overview

  • This study evaluates the effectiveness of different types of horse-derived antisera (monospecific, bispecific/monogeneric, and polyspecific/monogeneric) in neutralizing venoms from various sub-Saharan African snake species.
  • The goal is to identify immunization strategies that produce broad-spectrum antivenoms effective against multiple related snake venoms common to sub-Saharan Africa.

Background and Significance

  • Snakebite envenomation causes significant mortality and morbidity in sub-Saharan Africa.
  • Antivenoms are the primary treatment for snakebites, but current versions often target only specific venom types, limiting their effectiveness across diverse snake species.
  • Developing broad-spectrum antivenoms requires consideration of both the types of venoms used to immunize animals and the immunization protocols.
  • This study focuses on intrageneric neutralization scope—the ability of antivenoms to neutralize different venoms within the same genus.

Research Methods

  • Horses were immunized with different venom preparations to generate antisera:
    • Monospecific antisera: raised using venom from a single snake species.
    • Bispecific/monogeneric antisera: raised using venoms from two species within the same genus.
    • Polyspecific/monogeneric antisera: raised using venoms from multiple species within the same genus.
  • The venoms were from important sub-Saharan African snake genera: Bitis spp., Echis spp., Dendroaspis spp., spitting Naja spp., and non-spitting Naja spp.
  • Neutralization capacity was assessed using lethality neutralization assays in mice, evaluating protection against both homologous (same species) and heterologous (different species within the genus) venoms.
  • Spitting and non-spitting Naja species were analyzed separately due to their distinct venom types.

Key Findings

  • All types of antisera (mono-, bi-, and polyspecific) effectively neutralized the homologous venoms (i.e., the specific species used to generate them).
  • With one exception, these antisera also neutralized heterologous venoms within the same genus—meaning they could protect against different species despite targeted immunization.
  • Polyspecific antisera from Bitis, Echis, and Dendroaspis genera showed the broadest neutralization capacity across venoms of multiple species within these genera.
  • For spitting Naja venoms:
    • No significant difference in neutralizing ability was found among monospecific, bispecific, and polyspecific antisera.
    • This suggests that a monospecific immunogen from Naja nigricollis can provide wide neutralizing coverage within spitting Naja snakes.
  • For non-spitting Naja venoms:
    • Polyspecific antisera were generally more effective than monospecific antisera.
    • Notably, polyspecific antisera better neutralized venoms from Naja melanoleuca and Naja nivea than monospecific antisera did.

Conclusions and Practical Implications

  • Using polyspecific venom mixtures (multiple species from the same genus) to immunize horses is the best strategy to generate antivenoms with broad neutralization capacity for Bitis, Echis, Naja (non-spitting), and Dendroaspis genera—key snake groups in sub-Saharan Africa.
  • For spitting Naja snakes, immunization with a single species venom (Naja nigricollis) is sufficient to produce antivenoms with wide neutralizing power across the spitting cobra species.
  • These insights inform the design of more effective antivenoms tailored to the venom diversity found in sub-Saharan African snakes, improving treatment outcomes for snakebite victims.
  • Incorporating these findings into antivenom manufacturing could enhance the coverage and efficacy while potentially reducing production complexity and costs.

Cite This Article

APA
Sánchez A, Durán G, Segura Á, Herrera M, Vargas M, Villalta M, Arguedas M, Moscoso E, Umaña D, Gómez A, Gutiérrez JM, León G. (2024). Comparison of the intrageneric neutralization scope of monospecific, bispecific/monogeneric and polyspecific/monogeneric antisera raised in horses immunized with sub-Saharan African snake venoms. PLoS Negl Trop Dis, 18(5), e0012187. https://doi.org/10.1371/journal.pntd.0012187

Publication

PLoS neglected tropical diseases
ISSN: 1935-2735
NlmUniqueID: 101291488
Country: United States
Language: English
Volume: 18
Issue: 5
Pages: e0012187
PII: e0012187

Researcher Affiliations

Sánchez, Andrés
  • Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica.
Durán, Gina
  • Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica.
Segura, Álvaro
  • Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica.
Herrera, María
  • Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica.
Vargas, Mariángela
  • Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica.
Villalta, Mauren
  • Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica.
Arguedas, Mauricio
  • Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica.
Moscoso, Edwin
  • Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica.
Umaña, Deibid
  • Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica.
Gómez, Aarón
  • Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica.
Gutiérrez, José María
  • Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica.
León, Guillermo
  • Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica.

MeSH Terms

  • Animals
  • Horses / immunology
  • Antivenins / immunology
  • Antivenins / administration & dosage
  • Mice
  • Neutralization Tests
  • Africa South of the Sahara
  • Antibodies, Neutralizing / immunology
  • Antibodies, Neutralizing / blood
  • Snake Venoms / immunology
  • Immune Sera / immunology
  • Elapid Venoms / immunology
  • Snake Bites / immunology

Conflict of Interest Statement

I have read the journal’s policy and the authors of this manuscript have the following competing interests: The authors work at Instituto Clodomiro Picado, where an antivenom for use in sub-Saharan Africa is manufactured.

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Citations

This article has been cited 1 times.
  1. Sánchez A, Durán G, Cerdas M, Gutiérrez J, Segura Á, Herrera M, Vargas M, Sánchez A, Sánchez P, Solano G, Villalta M, Moscoso E, Umaña D, Arguedas M, Gómez A, Gutiérrez JM, León G. A polygeneric immunogen composed of 22 venoms from sub-Saharan African snakes to expand the neutralization scope of the EchiTAb-plus-ICP antivenom.. Toxicon X 2024 Dec;24:100213.
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