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Enhancing the Bothropic Antivenom through a Reverse Antivenomics Approach.

Tassia Chiarelli1, Jackelinne Y Hayashi1, Nathalia da Costa Galizio2

  • 1Departamento de Bioquímica, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo 04023-901, Brazil.

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|January 22, 2025
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Summary
This summary is machine-generated.

Researchers improved snakebite antivenom by enriching toxin-specific antibodies and reducing serum proteins. This enhanced antivenom (iBAv) shows greater potency and reduced non-specific proteins for treating Bothrops snakebites.

Keywords:
Bothrops jararacaaffinity chromatographyantivenomproteomicsreverse antivenomicssnakebite

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Area of Science:

  • Immunology
  • Biochemistry
  • Pharmacology

Background:

  • Antivenoms are crucial for treating snakebite envenomation but can cause adverse reactions due to non-specific antibodies and serum proteins.
  • Current animal-derived antivenoms, while life-saving, contain impurities that necessitate improvement for enhanced safety and efficacy.

Purpose of the Study:

  • To develop an improved bothropic antivenom (iBAv) by enriching toxin-specific antibodies and depleting serum proteins.
  • To enhance the potency and reduce the immunogenic components of antivenom against *Bothrops jararaca* venom.

Main Methods:

  • Affinity chromatography using immobilized *Bothrops jararaca* venom toxins to capture specific antibodies.
  • Proteomic analysis to quantify serum protein depletion (albumin and others).
  • Surface plasmon resonance (SPR) to assess toxin-binding affinity and *in vivo* studies to determine median effective dose (ED50).

Main Results:

  • The improved antivenom (iBAv) showed an 87% depletion in albumin and 37-83% reduction in other serum proteins compared to the original bothropic antivenom (BAv).
  • iBAv exhibited a 2.9-fold higher affinity for venom toxins and a 2.8-fold lower *in vivo* ED50, indicating significantly enhanced neutralizing potency.
  • The purification process successfully enriched neutralizing antibodies while removing non-specific serum proteins.

Conclusions:

  • Enriching specific antibodies and depleting serum proteins in antivenom reduces the total protein dose and increases potency.
  • This affinity-enriched antivenom represents a significant advancement in improving efficacy against *Bothrops jararaca* envenomations.
  • Further development is needed for large-scale implementation, but the approach offers a promising strategy for next-generation antivenoms.