HIV infection continues to spread rapidly via heterosexual transmission, as well as by vertical transmission from mother to newborn child. There is an urgent need to develop appropriate mucosal immunization strategies which have the potential to decrease the rate of acquisition through heterosexual and vertical transmission. The aim of this collaborative group is to define effective mucosal vaccine strategies for induction of protective anti-HIV envelope secretory IgA on rectal and female genital mucosal surfaces. Preliminary data in mice and primates have demonstrated that optimal mucosal immune responses in the rectum and cervix are produced through site-specific mucosal immunization. It is critical that similar studies be carried out among HIV- and HIV+ women including HIV+ women with high and lower CD4 counts. The oral recombinant cholera B subunit-killed whole cell vaccine has proven to be immunogenic and safe in studies in volunteers in North American and Europe, and does not pose a significant risk to HIV-infected women. The purpose of Project 2 is to investigate possible strategies to mucosal antigen (cholera toxin subunit B) and to HIV-1-envelope related antigens in humans and nonhuman primates. The Specific Aims of this project are: 1) to investigate optimal immunization strategies utilizing oral, rectal and vaginal routes to induce specific secretory IgA in rectal and cervical mucosa in primates and in HIV+ and HIV- women, using cholera toxin B subunit as a model mucosal antigen; 2) to define optimal mucosal delivery and adjuvant systems for HIV recombinant gp120/160 antigens, utilizing subhuman primates and mucosal immunizations: 3) to evaluate the most promising mucosally-targeted HIV or HIV-CTS combination vaccine in HIV+ and HIV- women, for induction of specific secretory IgA on cervical and rectal mucosal surfaces.