Sexual transmission of HIV is the most common route of HIV dissemination throughout most of the world. A vaccine capable of preventing sexual transmission of HIV would provide a reliable and straightforward method for stopping the AIDS pandemic. We have shown that live-attenuated SHIV inoculation can protect rhesus macaques from subsequent challenge with SIVmac239. Thus, protection from vaginal SIV challenge is attainable. In this project, we will use the monkey model to test routes of immunization for candidate 2 component HIV vaccine. We will judge the outcome of the experiments based on strength of the immune response to the route of administration and outcome of challenge with pathogenic SHIV. We will compare the immune responses of monkeys and humans immunized with the same vaccine, administered by the same route and according to the same schedule. Thus, we will directly compare the immune response of rhesus monkeys and humans. Regardless of the efficacy of the vaccine we test, at the end of these experiments we will know if HIV vaccine studies in rhesus monkeys reasonably predict the strength and nature of human immune responses.