ORIGINAL ARTICLE: Estradiol Limits Viral Replication Following Intravaginal Immunization Leading to Diminished Mucosal IgG Response and Non‐sterile Protection Against Genital Herpes Challenge

PROBLEM: Previously we reported that ovariectomized (OVX) mice receiving estradiol (E) prior to immunization with an attenuated strain of HSV-2 (TK-HSV-2) were not protected. Lack of protection in the E group was because of the inability of TK-HSV-2 to penetrate the thick keratinized epithelium. In this study, we determined the outcome of immunization after the thickening of vaginal epithelium following E-treatment waned. OVX, C57BL/6 mice were given Progesterone (P), E or saline (S) for 3 days and immunized with IVAG TK-HSV-2. METHOD OF STUDY: To determine the time point at which E-treated mice could be successfully immunized, the mice were inoculated with TK-HSV-2 between days 1 and 7 (ED1-ED7) post-E-treatment and challenged with IVAG HSV-2 three weeks later. RESULTS: The level of infection post-immunization correlated with HSV-2-specific IgG antibody level, which correlated with sterile protection. No viral infection was observed in ED1-ED3 groups and no specific antibodies were detected, resulting in no protection. Moderate infection was seen in ED5 group, resulting in low antibody production and non-sterile protection in 87.5% of mice. High antibody titers and sterile protection were observed in all groups that experienced robust infection post-immunization. CONCLUSION: The results show that estradiol leads to limited viral replication and diminished mucosal IgG response, resulting in non-sterile immune protection against genital herpes infection.