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.
Highlights
IntroductionSnakebite is is aa serious menace in in tropical tropical countries and was was recognized recognized as as a Snakebite serious menace countries and a “neglected “neglected tropical tropical disease” by the World HealthOrganization in [1].Every year, more than1.8–2.7 million cases disease” by the World Health Organization in 2017 [1]
Validated safety in humans: As many of these small molecule inhibitors have been evaluated for their toxicity in human recipients, they have already been proven sufficiently safe for use in the treatment of snakebite envenoming
For more than 100 years, animal-derived antivenoms have been the most accepted treatment for snakebite victims (Figure 1A). They significantly reduce mortality and morbidity, these antiquated antivenoms are beset with inherent limitations, including a high propensity to cause adverse reactions, complex manufacturing processes, low content of toxin-neutralizing antibodies, and an inability to effectively neutralize locally-acting toxins in distal tissues
Summary
Snakebite is is aa serious menace in in tropical tropical countries and was was recognized recognized as as a Snakebite serious menace countries and a “neglected “neglected tropical tropical disease”. More than 1.8–2.7 million cases of of snakebite envenoming in human victims occur, resulting in 80,000–140,000 deaths attwice least snakebite envenoming in human victims occur, resulting in 80,000–140,000 deaths and atand least twice as many disabling morbidities around the world [2]. India find India a sustainable solution to solution the Indian snakebite snakebite envenoming challenge Scientific discussions at this event concluded in agreement that the envenoming challenge. Schematic overview overview of of the plasma-derived antivenoms are manufactured through a five-step process. Snakes areare milked to plasma-derived antivenoms are manufactured through a five-step process. (4) The oligoclonal be combined to formulate an oligoclonal mixture monoclonal antibodies that each target different antibody mixture manufactured using mixture cell cultivation techniques, suchcell as single-batch expression key toxins. Drawbacks conventional plasma-derived and the corresponding benefits of antivenom is bottledof and ready for use. The corresponding benefits of recombinant antivenoms are presented in the right side of the figure
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