The long-term project objective is the commercialization of a safe, effective, easy to use, and painless polynucleotide vaccine delivery system that can be used in polynucleotide vaccines for biodefense against NIAID Category A, B and C Pathogens. Polynucleotide vaccines are on the forefront of vaccine BIOHAZARD development. They are important because of the fast development times possible and because cell mediated immune responses can be induced. The delivery system proposed here would be effective for most polynucleotide vaccines. This delivery system specifically addresses the requirement as presented in the NIAID Strategic Plan for Biodefense Research, February 2002, page 8. In addition to Biodefense, this system will provide effective polynucleotide vaccine delivery for less lethal viruses, some cancers and some third world diseases. The defense and commercial applications are extensive. The polynucleotide vaccine delivery system described here uses a microneedle array with the polynucleotide coated right on the needle in the array. There are hundreds of needles each about 0.15 mm long. This array is inserted into the skin with the needle penetrating to about the basal lamina. After insertion the polynucleotide leaves the needle surface and an electric field is used to permeabilize dendritic and epithelial cell membranes to permit the polynucleotide to enter the cell. The system will be tested with the WRAIR/Cyto Pulse dengue DNA vaccine, which will be used as a model for hemorrhagic fever viruses. The specific aims of this project are to design and develop to FDA QSR Standards the vaccine delivery system prototype, test for safety and efficacy in mice, and to test for safety in a Phase I human trial.