Development of effective immunotherapies for the treatment of HIV-1 infection will require induction of immune responses capable of irradicating the reservoirs of infection in infected individuals. This will require the stimulation of cellular immune responses capable of eliminating infected cells. Deliver of antigen and adjuvants in a manner that induces effective, antigen-specific cellular immune responses is a critical challenge for the design of immunotherapies for HIV-1 infection. Several cutaneous antigen delivery technologies are under development and show considerable promise, including protein-based and genetic immunization strategies. Establishment and maintenance of effective CTL-mediated immune responses general depends on the presence of CD4+ T-cell help, and a Th1 type response is important for optimal induction and maintenance of cell-mediated immunity. Using murine models, we propose experiments to genetically engineer the cutaneous microenvironment to favor the generation of Th1 type HIV specific immune responses. We will evaluate and compare the effect of co-delivery of plasmid constructs encoding cytokine adjuvants on the function of antigen presenting dendritic cells, and the nature of the immune response generated against expressed HIV antigens.
