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Toxins (Basel). 2018 Dec 13;10(12). pii: E534. doi: 10.3390/toxins10120534.

Biosynthetic Oligoclonal Antivenom (BOA) for Snakebite and Next-Generation Treatments for Snakebite Victims.

Author information

1
Department of Biological Sciences, National University of Singapore, 14 Science Drive 4, Singapore 117543, Singapore. dbskinim@nus.edu.sg.
2
Department of Molecular Genetics, The Donnelly Centre, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada. sachdev.sidhu@utoronto.ca.
3
Department of Biotechnology and Biomedicine, Technical University of Denmark, DK-2800 Kongens Lyngby, Denmark. ahola@bio.dtu.dk.

Abstract

Snakebite envenoming is a neglected tropical disease that each year claims the lives of 80,000⁻140,000 victims worldwide. The only effective treatment against envenoming involves intravenous administration of antivenoms that comprise antibodies that have been isolated from the plasma of immunized animals, typically horses. The drawbacks of such conventional horse-derived antivenoms include their propensity for causing allergenic adverse reactions due to their heterologous and foreign nature, an inability to effectively neutralize toxins in distal tissue, a low content of toxin-neutralizing antibodies, and a complex manufacturing process that is dependent on husbandry and procurement of snake venoms. In recent years, an opportunity to develop a fundamentally novel type of antivenom has presented itself. By using modern antibody discovery strategies, such as phage display selection, and repurposing small molecule enzyme inhibitors, next-generation antivenoms that obviate the drawbacks of existing plasma-derived antivenoms could be developed. This article describes the conceptualization of a novel therapeutic development strategy for biosynthetic oligoclonal antivenom (BOA) for snakebites based on recombinantly expressed oligoclonal mixtures of human monoclonal antibodies, possibly combined with repurposed small molecule enzyme inhibitors.

KEYWORDS:

antivenom; neglected tropical diseases; next-generation antivenom; recombinant antivenom; small molecule inhibitors; snakebite envenoming

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