HIV has multiple portals of entry through both the lower and upper female reproductive tract (FRT). Once deposited in the vagina, HIV, like sperm and radio-opaque dyes, moves rapidly from the vagina and ectocervix into the endocervix, uterus, and Fallopian tubes. Immune cells in the FRT are phenotypically and functionally distinct from blood cells in that they are hormonally controlled to support sperm migration, fertilization and implantation. Moreover, menstrual cycle-dependent variations in populations of immune-relevant cells and molecules in the female reproductive tract increase susceptibility to infection by pathogens.
Dartmouth researchers have now found that modulation of endogenous populations of cells through sex hormone (e.g., estradiol/progesterone) modifiers, compensation through endogenous or exogenous antigens or engineered hormone-responsive microbes, or direct stimulation, addition, or suppression of specific immune-relevant cells and molecules reduces or eliminates this susceptibility and specifically reduces the rate of infections that are transmitted via the FRT. Specifically, it has been found that Selective Estrogen Receptor Modulators (SERMs), TGF-beta inhibitors, glucocorticoids and engineered Lactobacillus can be used to optimize endogenous immune protection throughout the FRT thereby providing sustained protection throughout the menstrual cycle, and reversing the midcycle hormone-dependent suppression of immune function that places women at risk for infection by pathogens such as HIV-1.
This technology is claimed in the published PCT Application No. PCT/US2009/044767. We are seeking an industrial partner interested in its commercialization. (Ref: J456)
Last Updated: 7/24/12