ANTI-IDIOTYPE VACCINES AGAINST FLAVIVIRUSES

THE GOAL OF THIS RESEARCH IS THE DEVELOPMENT OF A MURINE MONOCLONAL ANTI-IDIOTYPE VACCINE 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 (AB1) THAT RECOGNIZES A CROSS-PROTECTIVE GROUP-REACTIVE DETERMINANT ON THE ENVELOPE GLYCOPROTEIN OF FLAVIVIRUSES. THE SPLEENS OF AB1-IMMUNIZED MICE WILL BE USED AS A SOURCE OF CELLS TO PRODUCE HYBRIDOMAS SECRETING MONOCLONAL ANTIBODIES DIRECTED AGAINST THE HYPERVARIABLE REGION OF AB1 (INTERNAL IMAGE ANTI-IDIOTYPE ANTIBODIES, AB2 ). AB2 WILL BE CHARACTERIZED BY ELISAAND BY IMMUNOBLOTTING, AND FOR INHIBITORY ACTIVITY IN A PLAQUE REDUCTION NEUTRALIZATION ASSAY. AB2 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.