PARTICLE-MEDIATED NUCLEIC-ACID IMMUNIZATION

Nucleic acid immunization involves the direct in vivo administration o f antigen-encoding plasmid DNA molecules that results in the de novo p roduction of correctly folded microbial antigens at the site of DNA de livery. While this process can lead to the development of neutralizing antibody responses recognizing authentic protein conformations, in vi vo antigen production also results in epitope presentation via the MHC class I antigen processing pathway, leading to the elicitation of cyt otoxic cellular immune responses. Recent efforts in the authors' labor atories have focused on use of the Accell(R) gene delivery system (gen e gun) to achieve the direct, intracellular delivery of small quantiti es of DNA into cells of the epidermis. The gene gun approach to nuclei c acid vaccination capitalizes on the synergistic combination of an ef fective DNA delivery system and a target tissue that Serves as a major immunological inductive site. Experimental gene gun-based nucleic aci d vaccines can achieve potent humoral and cytotoxic cellular immune re sponses in rodent models following immunization with as little as 16 n g of DNA, Equally strong responses have also been elicited in larger a nimals, such as pigs and monkeys, following epidermal immunization wit h as little as 2 to 4 mu g of DNA.