Recombinant Neutralizing Antibodies, A New Generation of Antivenoms

Biotechnological Trends in Spider and Scorpion Antivenom Development

“…Modern biotechnological techniques for the generation, isolation, and production of monoclonal antibodies (mAbs) or antibody fragments have recently been applied in the experimental development of next generation antivenoms against scorpion stings and spider bites (see Table 6, Table 7, and Table 8) [9]. The first reported neutralizing mAb in this field (mAb 4C1) was directed against the venom of the Androctonus australis hector (Aah) scorpion [146], and it was generated using hybridoma technology [147].…”

“…Increasing interest and efforts exist within the generation of recombinant, human antibody fragments using phage display technology [9]. The benefits of using phage display technology include the possibility of modifying the antibodies or fragments by genetic engineering techniques or affinity maturation by directed evolution.…”

“…Given that less medically relevant toxins in scorpion and spider venoms are essential to neutralize compared to snake venoms [9], and given the more laborious venom extraction procedures required for current scorpion and spider antivenom production, introduction of recombinant production methods for oligoclonal human antibodies or fragments thereof may indeed be a promising possibility, which is likely to be both feasible, cost-competitive [185], and which may yield more efficacious serum-free antivenoms with better safety profiles [11,128]. Coupled to powerful discovery platforms, such as phage display selection or the use of humanized animals, recombinant expression technologies could revolutionize the field of antivenoms by delivering safer, more efficacious therapies that are affordable for the healthcare systems of the developing world.…”

“…Currently, there are 19 antivenoms for human use and one antivenom for animal use on the market for scorpion stings, whereas only 10 antivenoms are used clinically for the treatment of spider bites (see Table 1 and Table 2, respectively). All of these antivenoms are of equine origin, and although they are effective in neutralizing scorpion and spider venoms, such animal-derived antisera suffer from significant drawbacks due to the heterologous nature of the proteins present in the antisera, which may elicit both early and late adverse reactions in human recipients [8,9]. Additionally, only a subset of the antibodies or antibody fragments present in these antivenoms have a therapeutic value since the presence of non-toxic immunogens in the venoms used for immunization may elicit therapeutically irrelevant antibodies in the immunized animal.…”

“…Finally, due to the very minute amounts of venom that can be extracted from scorpions and spiders, production of antisera against scorpion stings and spider bites is dependent on a highly laborious venom collection process, where large numbers of spiders and scorpions need to be milked (under microscope for spiders) in order to procure enough venom for immunization [12]. These challenges warrant technological innovation, not only to obtain safer and more effective antivenoms, but also to establish more sustainable productions processes that are independent of both venoms and animals [9]. …”