Challenges for vaccination against sexually-transmitted diseases: induction and long-term maintenance of mucosal immune responses in the female genital tract.
The ability to develop vaccines capable of preventing or protecting against sexually transmitted viruses, such as herpes simplex virus (HSV) and HIV is likely to depend on the induction of long-term mucosal immune responses. We have utilized a recombinant adenovirus capable of expressing HSV glycoprotein B (AdgB8) to demonstrate that intranasal (i.n.) immunization induces HSVgB-specific IgG and IgA antibodies in the serum and vaginal washes of mice. In contrast, systemic immunization only resulted in IgG antibodies in vaginal fluids. We also observed that although i.n. and i.p. AdgB8 immunization induced short-term CTL responses, only i.n. immunized mice maintained long-term CTL responses in the genital-associated lymphoid tissues. When compared to systemic immunization, mice immunized i.n. with the same dose of AdgB8 were better protected for a longer time period from a lethal intravaginal HSV-2 challenge. Protection occurred despite the fact that mice were initially infected (i.e. not sterile immunity) and the enhanced survival occurring in i.n. immunized mice correlated with the presence of HSVgB-specific IgA antibody-secreting cells in the genital tissues and with memory CTL, recall responses. Together, these results indicate that mucosal immunization is important for the induction and long-term maintenance of mucosal immune responses.