Monoclonal Antibodies to Prevent Use of Mycotoxins as Biological Weapons

摘要

Aflatoxin exposure causes a broad range of adverse effects including acute hepatic failure hepatic carcinoma and immunosuppression. The ability to weaponize aflatoxins has already been demonstrated raising concern that these potent agents might be used for biowarfare or agroterrorism. Passive antibody therapy is used for the treatment of toxin exposures and its potential for use in the event of bioterrorism has been highlighted. Monoclonal antibodies have been made to afiatoxins but currently none have been demonstrated to neutralize the adverse effects of exposure. The research goal is to generate monoclonal antibodies to aflatoxins for study of their potential to prevent disease. We generated a novel aflatoxin conjugate using keyhole limpet hemocyanin as a carrier and used this conjugate to immunize rats. We found that vaccination by either the intraperitoneal or subcutaneous route induced very high aflatoxin BI- binding antibody titers that were completely competed by free aflatoxin BBI in solution. We will make and characterize monoclonal antibodies to aflatoxins BI and GI and test them for their ability to inhibit cytotoxicity to rat hepatocytes and macrophages in vitro. Protective MAbs would subsequently be further developed for passive therapy in humans in the event that aflatoxins are used as agents of biowarfare.