Repetitive and consistent cervicovaginal exposure to certain viral pathogens appears to protect against their sexual acquisition in some women: potential mechanisms.

Several groups have proposed that human female promiscuity or polyandry, with repetitive and consistent cervicovaginal exposure to human immunodeficiency virus type 1 (HIV-1), can lead to protection against sexual acquisition of HIV-1 in some of these women. The mechanism of this phenomenon, the highly exposed persistently HIV-seronegative (HEPS) state, is unknown. Thus far, it has been correlated with viral epitope-specific immune responses in only about half of the women evaluated. But when present, these responses decline rapidly following interruption of pathogen exposure, and correlate with prompt acquisition of HIV. I have extended the concept of HEPS to another sexually transmitted viral pathogen, human papillomavirus (HPV). Supporting clinical and immunological information were identified from a literature search using PubMed as well as several sets of epidemiological data, including longitudinal surveys of HIV-1 incidence among female commercial sex workers (CSWs) in Africa and Thailand, and follow-up of a Danish cohort of CSWs and a large group of Brazilian women, both at high risk for HPV infection. These studies suggest that male-to-female penile-vaginal transmission of at least two viruses, HIV-1 and HPV, is blocked by local mucosal responses, immunologic or otherwise, which require repetitive, uninterrupted exposure to pathogen. Exploration of the mechanisms underlying such ostensibly protective responses may facilitate development of STD vaccines.