Immunization for protection of the reproductive tract: A review

Problem: Local application of non-replicating antigens to the female reproductive tract is ineffective in stimulating the common mucosal immune system, and induces only weak genital antibody responses. Studies of immune responses to genital infections such as gonorrhea also support the concept that, lacking mucosal immune inductive sites, the reproductive tract is ill-equipped to mount effective immune responses. Method of study: Intranasal (i.n.) and intravaginal (i.vag.) routes of immunization of mice with a protein antigen coupled to cholera toxin (CT) B subunit, or genetically engineered as chimeric proteins with the A2/B sunbunits of CT or type II heat-labile enterotoxin, were compared for their ability to induce specific antibody responses in vaginal fluids, saliva, and serum. Results: Mice immunized i.n. developed substantially stronger vaginal immunoglobulin A (IgA) and immunoglobulin G (IgG) and serum IgG and IgA antibodies, than those immunized i.vag. which also failed to develop salivary antibodies. Vaginal antibody responses induced i.n. persisted for at least 1 year, and were recallable by booster immunization after a prolonged period. Conclusions: Such alternative strategies for inducing potent genital antibody responses offer the prospect of prophylactic immunization against genital infections. Further studies are required to evaluate their applicability to humans, and to comprehend the cellular and molecular mechanisms involved in delivering effective immune responses to the reproductive tracts.