Abstract
Purpose :
Routes of immunization differ among vaccines to maximize the efficacy of host immune protection in various pathogen-susceptible tissues. This study investigates how administration of a live-attenuated HSV-1 vaccine termed HSV-1 0ΔNLS in different tissues affects the quality of protection against an ocular HSV-1 challenge.
Methods :
Eight-week old outbred CD-1 mice were immunized with a single administration of HSV-1 0ΔNLS intramuscularly in the flank (FL), subcutaneously in the footpad (FP), or via the intranasal (IN) mucosal route. Naive mice and mice immunized using a prime-boost FP+FL regimen previously shown to be highly efficacious were utilized as experimental controls. Humoral immune responses were assessed in serum, and animals were subsequently ocularly infected with the LD50 inoculum of HSV-1 McKrae. Animals were surveyed for viral burden in the cornea and nervous system and lymphocyte proliferation in regional lymph nodes during acute infection (day 7 post-infection) as well as corneal neovascularization and latent virus at day 30 post-infection. One-way ANOVAs were used for statistical analysis; data reflect 2-3 independent experiments.
Results :
Serum neutralizing antibody titers were not detected in naive animals but were present in immunized mice such that FP + FL > IN = FP > FL. The neutralizing antibody concentrations correlated with viral shedding and titers in the corneas and trigeminal ganglia following challenge. Viral replication was only blocked in the nervous system of the FP and FP+FL groups. Lymphocyte proliferation was significantly elevated in the mandibular lymph nodes of the naive group—as expected, was noted to be moderate in the single-vaccine FL, IN, and FP, groups, but was largely subdued in the FP+FL group. Corneal neovascularization was only prevented in the FP+FL and IN vaccine groups.
No correlation was discerned between the predominant HSV-specific antibody isotype classes and serum neutralization activity. All routes of immunization led to a significant reduction in the amount of virus that establishes a latent infection, while the highest efficacy was observed in the FP+FL group.
Conclusions :
While a single vaccination mediates a degree of protective efficacy against HSV-1 ocular infection and resultant pathology, the prime-boost approach affords superior protection by eliciting higher concentrations of HSV-neutralizing antibodies.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.