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Toxicon: X2024; 24; 100213; doi: 10.1016/j.toxcx.2024.100213

A polygeneric immunogen composed of 22 venoms from sub-Saharan African snakes to expand the neutralization scope of the EchiTAb-plus-ICP antivenom.

Abstract: Recent research suggests that a polygeneric immunogen made from the venoms of the most medically important viperid and elapid snakes in sub-Saharan Africa could elicit a broader antibody response in horses compared to the current EchiTAb-plus-ICP antivenom, especially against neurotoxic elapid venoms. To test this, 25 horses that have been regularly immunized to produce this antivenom were reimmunized with an immunogen containing 22 venoms from various snake species from the genera , , , and both spitting and non-spitting . The plasma collected from these horses was processed using the caprylic acid method to produce an industrial-scale freeze-dried antivenom. The anti-lethal neutralization scope of this new formulation was then compared to that of EchiTAb-plus-ICP which is designed to target the venoms of , , , and . The results indicated that adding more venoms to the immunogen did not significantly enhance the neutralization of the lethal effect of viperid venoms (except for ) or of venoms of spitting cobras (except for ). However, incorporating additional venoms from non-spitting neurotoxic spp. and spp. improved the neutralization scope of EchiTAb-plus-ICP against these neurotoxic venoms. The antivenom generated showed a wider anti-lethal neutralizing scope, as compared to the standard EchiTAb-plus-ICP antivenom and constitutes a good candidate to be tested in clinical trials in sub-Saharan Africa.
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Publication Date: 2024-11-16 PubMed ID: 39640251PubMed Central: PMC11617979DOI: 10.1016/j.toxcx.2024.100213Google Scholar: Lookup
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  • Journal Article

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.

Overview

  • This study evaluated a new antivenom developed from a mixture of 22 snake venoms to see if it could neutralize a wider range of snake venom effects compared to the existing EchiTAb-plus-ICP antivenom used in sub-Saharan Africa.
  • The research aimed to enhance protection particularly against neurotoxic venoms from non-spitting elapid snakes, while assessing if there was improved efficacy against viperid and spitting cobra venoms.

Background

  • EchiTAb-plus-ICP antivenom: This is the current antivenom produced by immunizing horses with a limited number of snake venoms from viper and cobra species prevalent in sub-Saharan Africa.
  • Limitations: The existing antivenom has a narrower efficacy range, particularly lacking strong neutralization capacity against neurotoxic elapid venoms from non-spitting cobras and mambas.
  • Polygeneric immunogen concept: By formulating an immunogen containing venoms from multiple snake genera including viperids and elapids, the immune response in horses could potentially be broadened to cover a wider spectrum of venom toxins.

Study Design

  • Immunogen formulation: A mixture of 22 venoms was assembled from several medically important snake genera in sub-Saharan Africa:
    • Viperid snakes (including genera such as Echis and Bitis)
    • Elapid snakes including both spitting (Naja subgenus) and non-spitting cobras (Naja subgenus), and Dendroaspis species (mambas)
  • Horse immunization: 25 horses previously immunized for production of EchiTAb-plus-ICP were reimmunized using this polygeneric venom mixture.
  • Antivenom production: Plasma was collected from the horses and purified using the caprylic acid method to produce a freeze-dried, industrial-scale antivenom formulation.
  • Comparative neutralization testing: The lethal neutralization effectiveness of this new antivenom was tested against that of EchiTAb-plus-ICP against a variety of venoms.

Key Findings

  • Effect on viperid venoms: Adding more viperid venoms to the immunogen did not significantly improve lethal neutralization, except for some improvement noted against Bitis arietans venom.
  • Spitting cobra venoms: No significant enhancement in neutralizing venoms from spitting cobras was observed, except for some improvement against certain spitting Naja species.
  • Non-spitting neurotoxic elapids: Incorporating additional venoms from non-spitting neurotoxic cobras (Naja) and mambas (Dendroaspis) significantly enhanced the antivenom’s neutralization scope against these venom types.
  • Overall effect: The new antivenom formulation demonstrated a broader spectrum, particularly improving coverage against neurotoxic venom components lacking in the existing EchiTAb-plus-ICP antivenom.

Implications

  • Clinical potential: This broader-spectrum antivenom has promising potential to improve treatment outcomes for snakebite victims in sub-Saharan Africa, particularly for bites by neurotoxic snakes that are otherwise poorly neutralized.
  • Next steps: The new antivenom formulation is a strong candidate for clinical trials to verify its safety and efficacy in human populations at risk.
  • Manufacturing considerations: The study demonstrated production feasibility at industrial scale using established purification methods (caprylic acid), which supports potential for large-scale deployment if clinical trials succeed.

Summary

  • This research supports the concept that including a greater diversity of venom antigens in immunogen mixtures can selectively expand the neutralization capacity of produced antivenoms.
  • While improvements against viper and spitting cobra venoms were limited, substantial enhancement against neurotoxic elapid venoms addresses an important clinical gap.
  • The findings encourage further development and clinical evaluation to deliver more effective, polyvalent antivenoms in areas with diverse snake species and venom effects.

Cite This Article

APA
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. (2024). 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, 24, 100213. https://doi.org/10.1016/j.toxcx.2024.100213

Publication

Toxicon: X
ISSN: 2590-1710
NlmUniqueID: 101741983
Country: England
Language: English
Volume: 24
Pages: 100213
PII: 100213

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.
Cerdas, Maykel
  • Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica.
Gutiérrez, Jairo
  • 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.
Sánchez, Adriana
  • Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica.
Sánchez, Paola
  • Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica.
Solano, Gabriela
  • 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.
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.
Arguedas, Mauricio
  • 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.

Grant Funding

  • Wellcome Trust

Conflict of Interest Statement

The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Guillermo Leon reports financial support was provided by 10.13039/100010269Wellcome Trust. All authors work at Instituto Clodomiro Picado, where the two antivenoms used in this study were manufactured.

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