Exposure to infected semen is the primary route of HIV transmission. It is well established that semen is
immumodulatory, though which components of this complex fluid are responsible remains unclear.
Localized immunosuppression at the time of initial exposure to HIV could explain why it has proven
difficult to generate protective mucosal immune responses against the virus, even with vaccine
candidates that induced strong anti-HIV immunity in the bloodstream. Our finding that trillions of
microvesicles are secreted into each ejaculate led us to explore the exosomal compartment of semen as
a source of immunoregulation in the recipient mucosa. I have found that exosomes from semen (SE)
rapidly enter antigen-presenting cells, and carry substantial amounts of small RNA, including miRNA.
Many of the miRNA carried by these exosomes have known or predicted targets important to immune
responses or epithelial cell barrier function. Therefore, this proposal aims to investigate how SE
modulate cells of the female genital mucosa. I will measure the transcriptional changes in mucosal cells
exposed to SE, determine the impact of SE on antigen-specific memory T cell responses, and establish
whether these effects could result from delivery of specific SE-miRNA cargo to recipient cells.
Understanding how individual components of semen modulate the female genital mucosa will assist
current efforts to develop vaccines and microbicides that protect against HIV infection.