Biofactories Applied to Future Antivenom Production

Background: Accidents caused by the Loxosceles laeta spider constitute a health problem in South America. Envenomation can lead to severe systemic manifestations, eventually compromising the patient’s life. Most regional health authorities consider antivenom administration the basis of effective treatment in the most serious cases. The availability of spider venom is the primary bottleneck for antivenom production. Herein, we present a novel biotechnological approach, based on the expression of recombinant versions of the most relevant toxin in loxoscelism, sphingomyelinase D (SphD), in insect larvae (Spodoptera frugiperda). Methods: We produced two versions of SphD: one conserving its biological activities (wtSphD) and a second alternative that was designed to be genetically detoxified (dSphD). Two horses were subjected to three consecutive hyperimmunization cycles with dSphD. The horses’ plasma was extracted at the end of each cycle and used to produce Active Pharmaceutical Ingredients (APIs) of antivenoms at a pilot scale. Results: Dermonecrotic activity of wtSphD was completely neutralized with the sera obtained from one horse and partially with that of the other. In contrast, the APIs derived in both cases completely neutralized wtSphD dermonecrotic activity. Direct hemolysis of human red blood cells by wtSphD was also neutralized by sera and APIs. Conclusions: These results show venom replacement or complementation potential by recombinant dSphD produced in this novel platform.