ACCELL(R) PARTICLE-MEDIATED DNA IMMUNIZATION ELICITS HUMORAL, CYTOTOXIC, AND PROTECTIVE IMMUNE-RESPONSES

Accell(R) particle-mediated gene delivery technology was employed for the intracellular delivery of antigen-encoding expression vectors in e pidermal tissues in laboratory animals. Delivery of plasmid DNA-coated gold microparticles using the Accell gene delivery system resulted in de novo antigen expression in epidermal cells that stimulated the ind uction of antigen-specific humoral and cytotoxic cellular immune respo nses. Optimal DNA delivery conditions favoring maximal humoral respons es required the delivery of 5 x 10(7) micron-sized gold particles cont aining 300 plasmid copies per particle (80 ng of vector total) into a 4-cm(2) area of abdominal skin. Comparison of immune responses between animals that received intramuscular injections of relatively large qu antities of vector DNA (100 mu g) and those that received intracellula r deliveries of submicrogram quantities of the same DNA to the epiderm is demonstrated that the latter approach was considerably more effecti ve at eliciting strong humoral responses. In addition, cytotoxic cellu lar immune responses were elicited to HIV-1 gp120 following epidermal delivery of HIV-1 gp160 or gp120 expression constructs. A qualitative shift from predominantly cytotoxic cellular to predominantly humoral i mmune responses with continued immunization indicated the potential fo r optimizing delivery conditions to favor specifically one type of res ponse over the other.