Enhancing the Bothropic Antivenom through a Reverse Antivenomics Approach

Author(s)

Chiarelli, Tassia ; Hayashi, Jackelinne Y. ; Galizio, Nathalia da Costa ; Casimiro, Fernanda M. S. ; Torquato, Ricardo ; Tanaka, Aparecida S. ; Morais-Zani, Karen de ; Tanaka-Azevedo, Anita M. ; Tashima, Alexandre K.

• Document type: Journal article
• Source: JOURNAL OF PROTEOME RESEARCH; v. 24, n. 2, p. 10-pg., 2025-01-22.

Abstract

Antivenoms are the only effective treatment for snakebite envenomation and have saved countless lives over more than a century. Despite their value, antivenoms present risks of adverse reactions. Current formulations contain a fraction of nonspecific antibodies and serum proteins. While new 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. In this study, we improved the bothropic antivenom (BAv), by capturing toxin-specific antibodies through affinity chromatography using immobilized Bothrops jararaca venom toxins. This process produced an improved antivenom (iBAv) enriched in neutralizing antibodies and depleted of serum proteins. Proteomic analysis showed that iBAv was 87% depleted in albumin and 37-83% lower in other serum proteins compared to BAv. Functional evaluation demonstrated that iBAv had a 2.9-fold higher affinity for venom toxins by surface plasmon resonance and a 2.8-fold lower ED50 in vivo, indicating enhanced potency. Our findings indicate that enriching specific antibodies while depleting serum proteins reduces the total protein dose required and increases the potency of antivenom. Although technical and economic considerations remain for large-scale implementation, this affinity-enriched antivenom represents a significant advancement in improving antivenom efficacy against B. jararaca envenomations. (AU)

• FAPESP's process: 24/02642-4 - Venom ontogenetic profile and bioprospecting potential of the three-finger toxins of the Naja kaouthia snake
• Grantee: Anita Mitico Tanaka-Azevedo
• Support Opportunities: Regular Research Grants
• FAPESP's process: 22/13850-1 - Immunological response to SARS-CoV-2 vaccination: from RNA to protein
• Grantee: Jackelinne Yuka Hayashi
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 17/21052-0 - Sepsis: mechanisms, therapeutic targets and epidemiology
• Grantee: Reinaldo Salomão
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 13/07914-8 - FoRC - Food Research Center
• Grantee: Bernadette Dora Gombossy de Melo Franco
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 21/05975-6 - Anti-SARS-CoV-2 antibodies in the plasma of vaccinees: dynamics of humoral response, sequencing, expression and effectiveness of recombinants for therapy and diagnosis
• Grantee: Alexandre Keiji Tashima
• Support Opportunities: Regular Research Grants
• FAPESP's process: 21/07627-5 - Investigation of coagulotoxicity of snake venom species from Viperidae family of medical importance in Brazil.
• Grantee: Nathália da Costa Galizio
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 23/00670-8 - Unravelling the mechanism of snake venom induced haemorrhage by focusing on basement membrane disruption
• Grantee: Karen de Morais Zani
• Support Opportunities: Regular Research Grants
• FAPESP's process: 17/20106-9 - Peptidomics of Brazilian snake and spider venoms
• Grantee: Alexandre Keiji Tashima
• Support Opportunities: Regular Research Grants
• FAPESP's process: 20/07268-2 - Characterization of the coagulotoxic profile of venoms of Viperidae snakes with medical importance in Brazil
• Grantee: Karen de Morais Zani
• Support Opportunities: Regular Research Grants