Recombinant Neutralizing Antibodies, A New Generation of Antivenoms

Toxin Neutralization Using Alternative Binding Proteins

“…Raising a significant titer of antibodies against small venom components with low immunogenicity and high toxicity has been demonstrated to be particularly problematic [46,47,48,49]. Furthermore, the use of non-human antibodies results in a high risk of both early and late adverse reactions [50,51], such as serum sickness and anaphylactic shock, since these antibodies are immunogenic due to their heterologous nature. Finally, due to the very minute amounts of venom that can be extracted from many venomous animals (especially spiders and scorpions), production of antisera is dependent on laborious venom collection processes, where large numbers of animals need to be milked by electrostimulation in order to procure enough venom for immunization.…”

“…Finally, due to the very minute amounts of venom that can be extracted from many venomous animals (especially spiders and scorpions), production of antisera is dependent on laborious venom collection processes, where large numbers of animals need to be milked by electrostimulation in order to procure enough venom for immunization. Such challenges necessitate significant technological innovation for the production of safer and more effective antivenoms, as well as an increase in the economic sustainability of the production process itself, by making it independent of both venoms and animals [50,52].…”

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 ].…”

“…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 ].…”