Enhancing the Bothropic Antivenom through a Reverse Antivenomics Approach.

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.