Protection of the vaginal mucosae and sensory ganglia of immune mice against reinfection with herpes simplex virus type 2 (HSV-2)

We used an attenuated HSV-2 strain as a paradigm for a successful HSV vaccine to investigate the immune basis for protection of the vaginal mucosa and sensory ganglia. Antibody deficient HSV-immune mice and HSV-immune conventional mice depleted of T cells or T cell subsets were used to examine the immune mechanisms of protection. Virus was cleared from the vaginal mucosae of both antibody deficient- and control treated HSV-immune mice. By contrast, even in the presence of specific antibody, T cell-dependent mechanisms (primarily CD4+) were required for clearance of virus from the vaginal mucosae of HSV-immune mice and could be detected by 24 hours after intravaginal reinoculation. In contrast, optimal protection of the sensory ganglia against reinfection with HSV-2 required both HSV-specific antibody and T cells. Infectious HSV-2 could be recovered from the sensory ganglia of both antibody deficient- and T cell depleted- HSV-immune mice on days 6-8 after HSV-2 challenge. No virus was detected in the sensory ganglia or spinal cord of HSV-immune mice depleted of CD4+ or CD8+ T cells suggesting that the T cell mediated protection could be provided by either subset. Neutralization of IFN-g prior to challenge of HSV-immune mice resulted in diminished protection of the vaginal mucosa but not of the sensory ganglia. The results of this study suggest that the induction of T cell responses which can be rapidly recalled is an important consideration in the design of vaccines against HSV-2 for protection of both the vaginal mucosa and sensory ganglia.