Intranasal and subcutaneous immunization under the effect of estradiol leads to better protection against genital HSV-2 challenge compared to progesterone

This study examined the effect of hormonal environment on intranasal and subcutaneous routes of immunization in a genital herpes infection model. Ovariectomized mice were treated with estradiol (E2), progesterone (P4) or placebo hormone pellets and immunized intranasally (i.n.) or subcutaneously (s.c.) with attenuated HSV-2. Immunized mice were subsequently challenged, intravaginally, with wild-type HSV-2. Mice immunized under the influence of E2 showed higher survival rates, reduced pathology and significantly lower viral shedding compared with those immunized under the influence of P4 or placebo, by both i.n. and s.c. routes. Vaginal and serum anti-HSV-2 IgG, but not IgA, levels correlated with decreased pathology in E2-treated, i.n. immunized mice. We conclude that immunization under the influence of E2 afforded better protection compared to placebo and P4, by both routes of immunization. Female sex hormones can influence immune responses and outcome of viral challenge in the genital tract following systemic immunization.