Degree

Doctor of Philosophy (PhD)

Department

Pathobiological Sciences

Document Type

Dissertation

Abstract

Herpes simplex virus type-1 (HSV-1) can cause severe ocular infection and blindness. We have previously shown that the HSV-1 VC2 vaccine strain is protective in mice and guinea pigs against genital herpes infection following vaginal challenge with HSV-1 or HSV-2. In this study, we evaluated the efficacy of VC2 intramuscular vaccination in mice against herpetic keratitis following ocular challenge with the lethal human clinical strain HSV-1(McKrae). VC2 vaccination in mice produced superior protection and morbidity control in comparison to its parental strain HSV-1(F). Specifically, after HSV-1(McKrae) ocular challenge, all VC2- vaccinated mice survived, while 30% of the HSV-1(F)- vaccinated and 100% of the mock-vaccinated mice died post-challenge. VC2-vaccinated mice fully recovered from initial conjunctivitis. In contrast, both mock- and HSV-1(F)-vaccinated mice developed time-dependent progressive keratitis with corneal opacification, which was histologically characterized by severe stromal keratitis with immune cell infiltration and neovascularization in corneal stroma. Cornea in VC2-immunized mice exhibited significantly increased infiltration of CD3+ T lymphocytes and decreased infiltration of activated Iba1+ monocytes/macrophages in comparison to mock- or HSV-1(F)-vaccinated groups. VC2 immunization produced higher virus neutralization titers and higher HSV-1-specific IgG levels than HSV-1(F)-vaccination post-challenge. Furthermore, VC-vaccination significantly increased the CD8+ T effector memory (TEM) subsets and CD4+ T central memory (TCM) subsets in the draining lymph nodes in response to the ocular HSV-1 (McKrae) challenge than mock- or HSV-1(F)-vaccination. These results indicate that VC2 vaccination produces a robust humoral and cellular immune response to protect against HSV-1-induced ocular immunopathogenesis.

Date

5-14-2019

Committee Chair

Kousuolas, Konstantin

Available for download on Monday, May 11, 2026

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