New generation botropic antivenom: Mixture of monoclonal antitoxin antibodies

• Grant number: 23/04634-6
• Support Opportunities: Regular Research Grants
• Start date: December 01, 2023
• End date: November 30, 2025
• Field of knowledge: Health Sciences - Collective Health - Public Health
• Principal Investigator: Sonia Aparecida de Andrade Chudzinski
• Grantee: Sonia Aparecida de Andrade Chudzinski
• Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Associated researchers: Anita Mitico Tanaka-Azevedo ; Fátima Nogueira ; Fernanda Calheta Vieira Portaro ; Marisa Maria Teixeira da Rocha ; Wilmar Dias da Silva
• Associated scholarship(s): 24/08308-9 - Generation of monoclonal antitoxin antibodies from Bothrops atrox venom via hybridoma technology, BP.DR

Abstract

Snakebite affects more than two million people, causing around one hundred thousand deaths annually, and this number is four times higher when amputations and other sequelae are taken into account. The high mortality and incidence led the World Health Organization to categorize snakebites as a category A neglected tropical disease, the highest of the class. In Brazil, about 90% of cases are caused by snakes of the genus Bothrops; their venom is a highly complex mixture of proteins, peptides, and other factors that, when interacting with human proteins, trigger various symptoms. Among the most abundant toxins in the venom, metalloproteases, serine proteases and phospholipases A2 stand out. The treatment for envenoming is the administration of bothropic antivenom serum, produced in horses by the administration of sub-lethal doses of venom, although this treatment is highly effective to avoid lethality, it still has some limitations, such as the formation of immune complexes, partial neutralization of local hemorrhage and of serine proteases. With the evolution of recombinant technology and techniques for the discovery of monoclonal antibodies, with high specificity and avidity, a solution composed of neutralizing monoclonal antibodies specific for the main toxins present in the venom of snakes of the genus Bothrops, will be a driver for the development of next-generation antivenoms. That could be an alternative to the traditional technique of obtaining polyclonal antibodies through the immunization of animals. Therefore, this project aims at the purification and characterization of monoclonal, anti-hemorrhagin, anti-thrombin like (TLE2) and anti-phospholipases, BaPLA2 I and BaPLA2 III. In addition, to evaluate in a comparative form to commercial bothropic antivenom, the neutralizing efficacy of these mAbs, separately and in mixture, regarding the main effects of bothropic envenomation. (AU)