The human vagina is a principal entry and transmission site for sexually transmitted pathogens including HIV-1, yet little information is available concerning influences of endogenous and exogenous factors on vaginal mucosal immune defense mechanisms or other parameters affecting vaginal infection. We propose to test the hypothesis that reproductive hormones, intercourse and intravaginal products affect the transmission rate of HIV- 1 through alterations in vaginal defense mechanisms, specifically by: l) inhibition of vaginal humoral, cellular or innate immune defense mechanisms; 2) enhancement of susceptibility to pathogen infection through improved access to target cells and/or their activation, and/or 3) enhancement of HIV-1 production through activation of infected cells in the vagina. RT-PCR, ELISA and immunohistology techniques will be utilized to better define immune defense mechanisms of the normal human vagina. Lymphocyte and inflammatory cell populations, and their products (immunoglobulins, cytokines, activation and adhesion molecules) will be assessed in surgical specimens from various regions of the vagina and cervicovaginal lavage specimens (CVLs) obtained: 1) throughout the menstrual cycle, 2) throughout pregnancy and the postpartum period, 3) post menopause with and without estrogen replacement, 4) following intercourse or administration of seminal components, and 5) following administration of intravaginal products. Similar CVL data will be attained for HIV-1 infected women (WITS cohort) and correlated with HIV-1 titers in CVLs assessed by quantitative HIV culture and PCR methods. In addition, studies will be performed to further document effects of cervicovaginal secretions, taken from the conditions listed above, on immune function and HIV-1 infectivity in vitro. This study is designed to provide a foundation for the development of vaccines and other strategies against sexually transmitted pathogens.
