Female genital tract immunity: distinct immunological challenges for vaccine development

The population explosion and unintended pregnancies, sexually transmitted diseases including human immunodeficiency virus, and cervical cancer, are major challenges to health worldwide. Their prevention might be achieved through vaccination-based approaches to activate specific immunity against pathogen- or fertility-associated antigens in the female genital tract (FGT). This article aims to review methodologies for enhancing adaptive immunity in the FGT to maximize the response to vaccination. Most components of the adaptive and innate mucosal immune system are present in the FGT and several features are common with the nasopharynx/bronchial and gastrointestinal tracts. In contrast to other mucosal sites, the FGT has minimal local lymphoid tissue. Other sites primarily produce IgA and IgM while in the FGT, especially the vaginocervix, IgG is the predominant immunoglobulin secreted. In rodents, data exist to substantiate a common mucosal immune system interconnecting the nasal/bronchial, gastrointestinal, and female genital tracts. The intranasal route seems the most efficacious to induce an immunity in the FGT especially when combined with a systemic or parenteral route. In humans, for induction of secretory IgA and IgG antibodies in the FGT, immunization by the nasal or the vaginal route is effective. In vaginal immunization, a strong and consistent antibody response is best achieved following vaccination during the follicular phase of the menstrual cycle. Antibodies administered systemically percolate into the FGT and can provide immunoprotection against target molecules or cells. Thus, as well as active immunization using selected routes, the passive immunization approach may provide a viable alternative to vaccinology for future development.