Development and evaluation of a recombinant multi-epitopic protein (TsMEP) as an antigen candidate for Tityus serrulatus antivenom production

Abstract

Scorpionism is Brazil's most prevalent envenomation. Treatment typically involves the use of heterologous antivenoms derived from the immunization of horses with crude T. serrulatus venom (TsV). Due to the high toxicity of this immunogen, as well as the particular challenges associated with the use of venoms as antigens, there is interest in exploring new alternatives for reducing their use in antivenom production. In this study, ten linear B-cell epitopes from hyaluronidase and voltage-gated sodium channel toxins, previously identified using the SPOT-synthesis method, were selected to construct a recombinant chimeric MultiEpitopic Protein from T. serrulatus scorpion venom (TsMEP). We demonstrated that TsMEP is non-toxic, and antibodies elicited in rabbits against this antigen exhibited reactivity in ELISA with Brazilian T. serrulatus, T. bahiensis, T. obscurus, and T. stigmurus venoms, as well as with Peruvian Hadruroides lunatus and North African Androctonus australis hector scorpion venoms. In vivo and in vitro neutralization assays revealed that rabbit anti-TsMEP antibodies partially neutralize the hyaluronidase activity of T. serrulatus venom and its lethality. Data presented here suggests that this multiepitopic protein could be a promising candidate in experimental immunization approaches for antivenom production for clinical use against Tityus spp. venoms.