Vaccinia virus has proven safe and effective in eradicating smallpox, and has considerable promise as an expression vector for vaccine development. Its ability to accommodate more than 25 kilobases of exogenous DNA without impairing its ability to replicate, and, to present antigen(s) either intracellularly or on the surface of infected cells, as required, has been used successfully to identify or condirm the targets of and to stimulate specifically both cell-mediated and humoral immune responses. We plan to use vaccinia virus vectors to identify important HIV epitopes for vacccine development. Using novel techniques and promoters previously developed in our laboratories, we will construct novel vaccinia virus recombinant to express recombinant genes encoding multiple repeats of potent B cell and Th and Tc epitopes from single and multiple isolates of HIV. These recombinant vaccinia viruses will be assessed in a mouse model system for their ability to induce broadly reactive neutralizing antibody and CMI responses against multiple HIV variants. This approach should lead to the construction of novel, live recombinant vaccine candidates capable of providing protection against HIV infection.