Particle-mediated nucleic acid immunization.

Nucleic acid immunization involves the direct in vivo administration of antigen-encoding plasmid DNA molecules that results in the de novo production of correctly folded microbial antigens at the site of DNA delivery. While this process can lead to the development of neutralizing antibody responses recognizing authentic protein conformations, in vivo antigen production also results in epitope presentation via the MHC class I antigen processing pathway, leading to the elicitation of cytotoxic cellular immune responses. Recent efforts in the authors' laboratories have focused on use of the Accell gene delivery system (gene gun) to achieve the direct, intracellular delivery of small quantities of DNA into cells of the epidermis. The gene gun approach to nucleic acid vaccination capitalizes on the synergistic combination of an effective DNA delivery system and a target tissue that serves as a major immunological inductive site. Experimental gene gun-based nucleic acid vaccines can achieve potent humoral and cytotoxic cellular immune responses in rodent models following immunization with as little as 16 ng of DNA. Equally strong responses have also been elicited in larger animals, such as pigs and monkeys, following epidermal immunization with as little as 2 to 4 micrograms of DNA.