The long-term objective of the proposed research is to establish an effective form of vaccination to prevent HIV-1 infection. The general strategy, as presented, is to employ sensitized liposomes to encapsulate and deliver HIV-1-specific proteins to the gut lumen in order to elicit mucosal immunity. The use of liposomes has proven to be an efficient approach to elicit antigen-specific humoral responses, and more recently T cell immunity in the mucosa. The applicants propose to assess the feasibility of employing liposomes to elicit protective CD8+ T and CD4+ T cell responses specific for HIV-1 encoded proteins. Specifically, liposomes containing HIV-specific gag (pr55gag) will be used to target M cells of Peyer's patches of mice transgenic for a chimeric HLA-A2.1/Kb molecule. The investigators will then determine the effectiveness of this approach to elicit: (i) CD8+ cytotoxic T cell (CTL) activity specific for known, HLA-A2.1 restricted, gag-specific epitopes, and (ii) CD4+ T helper cell reactivity. The proposed work is expected to provide the necessary insight to develop rational liposome-based vaccine strategies to establish effective mucosal immunity for the prevention of HIV-1 infection.