GENE GUN-BASED NUCLEIC-ACID IMMUNIZATION - ELICITATION OF HUMORAL ANDCYTOTOXIC T-LYMPHOCYTE RESPONSES FOLLOWING EPIDERMAL DELIVERY OF NANOGRAM QUANTITIES OF DNA

Particle-mediated (gene gun) DNA transfer to the epidermis was evaluat ed for its ability to elicit humoral and cytotoxic T lymphocyte respon ses using decreasing quantities of plasmid DNA-based antigen expressio n vectors. Using plasmids encoding human growth hormone, human alpha-1 -antitrypsin, and influenza virus nucleoprotein, strong immune respons es were observed in mice following immunization with as little as 16 n g of DNA using an electric discharge gene delivery system. Significant antibody titers were observed against these antigens following a prim ary immunization, with responses rising dramatically following a boost . Increasing the DNA dose above 16 ng per immunization had little bene ficial effect. In contrast to particle-mediate DNA delivery, intramusc ular or intradermal inoculation required greater than 5000-fold more D NA to achieve comparable results. Data are also presented demonstratin g that a simple, hand-held version of the Accell(R) DNA delivery syste m, employing compressed helium as the particle motive force, achieves immune responses comparable to the traditional electric discharge devi ce.