DNA Vaccine Delivery System for Biodefense with dengue

DESCRIPTION (provided by applicant): The long-term objective is the commercialization of a safe, effective, easy to use and painless polynucleotide vaccine delivery system that can be used in vaccines for biodefense against NIAID Category A, B and C pathogens. In addition to biodefense related vaccines, the Easy Vax vaccine delivery system which is the subject of this commercialization project can be used in other infectious disease and cancer vaccines. The specific vaccine being developed for delivery by the Easy Vax vaccine delivery system is a dengue vaccine. Dengue is a virus specifically mentioned in the NIAID Strategic Plan for Biodefense Research. The polynucleotide vaccine delivery system called Easy Vax, uses a microneedle array coated with the vaccine directly on the needles of the array. There are hundreds of needles, each less than 0.5 mm long. The array is inserted into skin using a device that contains an insertion mechanism and electronics. The needles penetrate at least to the basal lamina of skin, adjacent to target cells such as skin Langerhans cells and epithelial cells. After insertion, the vaccine polynucleotide leaves the needles and is available for delivery into cells. Brief electrical pulses, delivered by the self-contained electronics deliver the vaccine polynucleotide into cells. Once in cells, vaccine antigen is expressed and stimulates both humoral and cell mediated immunity. A dengue DNA vaccine is being developed for delivery by the Easy Vax vaccine delivery system. All work to date was done using dengue 1. Since there are four dengue serotypes and all need to be included in a commercial vaccine, vaccine plasmids need to be made for the remaining three serotypes. Dengue is a major public health problem in many tropical areas. Specific aims of this project are to produce a pilot production line for manufacture of the microneedle arrays, molecularly engineer the remaining three vaccine plasmids, test the tetravalent vaccine in mice and primates, safety test the vaccine and assess acceptance of the delivery system by humans. CONTINUATION OF PHASE II SBIR