Estradiol limits viral replication following intravaginal immunization leading to diminished mucosal IgG response and non-sterile protection against genital herpes challenge.
OBJECTIVE
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.


METHODS
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.


CONCLUSIONS
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.
Gillgrass
Amy
A
Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada.
Chege
Duncan
D
Bhavanam
Sudha
S
Kaushic
Charu
C
D000282:Administration, Intravaginal; D000818:Animals; D004958:Estradiol / Q000502:physiology*; D005260:Female; D006558:Herpes Genitalis / Q000276:immunology* / Q000517:prevention & control / Q000821:virology; D018258:Herpesvirus 2, Human / Q000276:immunology*; D007114:Immunization; D007074:Immunoglobulin G / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009092:Mucous Membrane / Q000276:immunology; D014779:Virus Replication
D007074:Immunoglobulin G; D004958:Estradiol