Induction of T cell immunity by cutaneous genetic immunization with recombinant lentivector

Recent studies suggest that T cell-based cellular immunity plays an important role in preventing and delaying progression of infectious and neoplastic diseases. Based on these findings, recent efforts in vaccine research are giving rise to a new generation of "T cell" vaccines. The development of T cell vaccines has been problematic. Current investigations are focusing on gene-based immunization strategies, including the development of non-viral "naked" plasmid DNA and recombinant viral vector-based genetic immunization approaches. Here, we briefly review recent progress in the development of recombinant viral vectors for genetic immunization and our own recent studies elucidating differences in mechanisms of genetic immunization. We propose that the mechanism of immune induction depends in part on unique features of specific viral vectors, and that a comparison of representative vectors mechanistically will enable a more informed understanding of the determining parameters of immune induction. Our initial studies have focused on the identification of antigen-presenting-cell subsets important for priming CD8+ T cell immunity, the effects of antigen persistence on immune responses, and the unique immunogenicity of skin as a target tissue for vaccine delivery. We review data suggesting that the unique properties of recombinant lentivectors make them appealing candidates as genetic immunization vehicles for eliciting T cell immune responses.