The goal of this SBIR proposal is the development of a murine monoclonal antiidiotype vaccine that will elicit neutralizing antibodies against the flavivirus group of arboviruses, in particular dengue types 1-4. In Phase 1, 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 antiidiotype antibodies, Ab2-gamma). Ab2-gamma will be characterized by ELISA, immunoblotting, and for inhibitory activity in a plaque reduction neutralization assay. Ab2-gamma will further be used to immunize mice to elicit antibodies reactive with native flavivirus E-glycoprotein (Ab3). These studies will lay the foundation for antitidiotype vaccine preclinical and clinical safety and efficacy trials in Phases II and III.
