Enhancing the bothropic antivenom through a reverse antivenomics approach

ABSTRACT: Antivenoms are the only effective treatment for snakebite envenomation and have saved countless lives over more than a century. Despite its value, antivenoms often present risks of adverse reactions. Current formulations contain a substantial fraction of non-specific antibodies and serum proteins that do not neutralize venom toxins. While new alternatives are being researched and promising candidates emerge as the next generation of antivenoms, it remains clear that animal-derived antivenoms will still play a critical role for years to come. And current antivenom formulations could still be optimized for safety and efficacy. In this study, we used a reverse antivenomics approach to improve the bothropic antivenom (BAv), capturing toxin-specific antibodies through affinity chromatography using Bothrops jararaca venom toxins immobilized on CNBr-activated resin. This process produced an improved antivenom formulation (iBAv) enriched in neutralizing antibodies and depleted of serum protein contaminants. Proteomic analysis showed that iBAv was 87% depleted in albumin and 37-83% lower in other serum proteins compared to the original BAv. Functional assessments demonstrated that iBAv had a 2.9-fold higher affinity for B. jararaca venom toxins via surface plasmon resonance and a 2.8-fold lower ED50 in vivo in a mice model, indicating enhanced potency and efficacy. Our findings suggest that enriching specific neutralizing antibodies while depleting serum proteins may reduce the overall protein dose required and potentially decrease the risk of adverse reactions. Although technical and economic considerations remain for large-scale implementation, this affinity-enriched antivenom formulation represents a significant advancement in enhancing antivenom efficacy against Bothrops jararaca envenomations.

INSTRUMENT(S): impact II

ORGANISM(S): Equus Caballus (ncbitaxon:9796)

SUBMITTER: Alexandre Keiji Tashima  

PROVIDER: MSV000096324 | MassIVE | Thu Nov 07 02:41:00 GMT 2024

SECONDARY ACCESSION(S): PXD057613

REPOSITORIES: MassIVE