Abstract
Snakes, scorpions, and spiders are venomous animals that pose a threat to human health, and severe envenomings from the bites or stings of these animals must be treated with antivenom. Current antivenoms are based on plasma-derived immunoglobulins or immunoglobulin fragments from hyper-immunized animals. Although these medicines have been life-saving for more than 120 years, opportunities to improve envenoming therapy exist. In the later decades, new biotechnological tools have been applied with the aim of improving the efficacy, safety, and affordability of antivenoms. Within the avenues explored, novel immunization strategies using synthetic peptide epitopes, recombinant toxins (or toxoids), or DNA strings as immunogens have demonstrated potential for generating antivenoms with high therapeutic antibody titers and broad neutralizing capacity. Furthermore, these approaches circumvent the need for venom in the production process of antivenoms, thereby limiting some of the complications associated with animal captivity and venom collection. Finally, an important benefit of innovative immunization approaches is that they are often compatible with existing antivenom manufacturing setups. In this review, we compile all reported studies examining venom-independent innovative immunization strategies for antivenom development. In addition, a brief description of toxin families of medical relevance found in snake, scorpion, and spider venoms is presented, as well as how biochemical, bioinformatic, and omics tools could aid the development of next-generation antivenoms.
Highlights
Snakes, scorpions, and spiders belong to a diverse group of venomous animals capable of causing severe envenomings through their bite or sting, which are considered a serious public health issue in many parts of the world [1,2,3]
We present a comprehensive overview of all studies testing innovative venom-independent immunization strategies for antivenom development
Immediate improvements are warranted, where innovative, venom-independent immunization approaches offer the potential of quick adaptability, as they are compatible with existing antivenom manufacturing setups
Summary
Scorpions, and spiders belong to a diverse group of venomous animals capable of causing severe envenomings through their bite or sting, which are considered a serious public health issue in many parts of the world [1,2,3]. Apart from leaving aside venom use and, the need to keep venomous animals in captivity, antivenom production based on new immunization approaches is considered quite feasible, since it can readily be adapted to current manufacturing platforms without introducing significant modifications. New immunization approaches may offer the possibility of exclusively using clinically relevant toxins for the immunization procedure, likely leading to a higher titer of therapeutically relevant antibodies and an increased antivenom neutralizing capacity. Such higher titers might, in turn, possibly result in safer products (with lower propensity to cause adverse reactions), as the total dosage of antibodies (which are heterologous proteins) required for venom neutralization would be lower. Novel approaches in the therapy of envenomings, such as the development of toxin inhibitors based on aptamers, small molecules, or recombinant antibodies (or fragments thereof) of human or camelid origin are beyond the scope of this review, and can be found elsewhere [32,33,34,35,36,37]
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