The goal of this research is the development of a murine monoclonal anti -i di o type va cc ine that will elicit neutralizing antibodies against the flavivirus group of arboviruses, in particular dengue types 1-4. In Phase I, mice will be immunized with a previously characterized murine monoclonal antibody (Abl) that recognizes a cross-protective group-reactive determinant on the envelope glycoprotein of flaviviruses. The spleens of Abl-immunized mice will be used as a source of cells to produce hybridomas secreting monoclonal antibodies directed against the hypervariable region of Abl (internal image anti-idiotype antibodies, Ab2Y). Ab2y will be characterized by ELISA and by immunoblotting, and for inhibitory activity in a plaque reduction neutralization assay. Ab2r will further be used to immunize mice to elicit antibodies reactive with native flavivirus E-glycoprotein (Ab3). These studies will lay the foundation for subsequent anti-idiotype vaccine preclinical and clinical safety and efficacy trials.Awardee's statement of the potential commercial applications of the research:A vaccine against flaviviruses such as dengue and Japanese encephalitis will have a large potential market. Diagnostic assays using monoclonal antibodies would have important clinical utility.National Institute of Allergy and Infectious Diseases (NIAID)
