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 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 did not exhibit any symptoms of ocular infection and completely recovered from initial conjunctivitis. In contrast, HSV-1(F)-vaccinated mice developed time-dependent progressive keratitis characterized by corneal opacification, while mock-vaccinated animals exhibited more severe stromal keratitis characterized by immune cell infiltration and neovascularization in corneal stroma with corneal opacification. Cornea in VC2-immunized mice exhibited significantly increased infiltration of CD3+ T lymphocytes and decreased infiltration of Iba1+ macrophages in comparison to mock- or HSV-1(F)-vaccinated groups. VC2 immunization produced higher virus neutralization titers than HSV-1(F) post challenge. Furthermore, VC-vaccination significantly increased the CD4 T central memory (TCM) subsets and CD8 T effector memory (TEM) subsets in the draining lymph nodes following ocular HSV-1 (McKrae) challenge, then mock- or HSV-1(F)-vaccination. These results indicate that VC2 vaccination produces a protective immune response at the site of challenge to protect against HSV-1-induced ocular pathogenesis.
Highlights
Herpes Simplex Virus (HSV) -1 and -2 are highly prevalent human pathogens
It has been estimated that 67% and 11% of world population are infected with Herpes simplex virus type-1 (HSV-1) and HSV-2, respectively [2, 3], while 33% of the population is estimated to have a latent infection with HSV-1[4]
Our findings suggest that VC2 immunization induces a significantly improved immune response compared to its parental HSV-1(F) wild-type strain, they both protect the mice from lethal challenge, characterized by increased production of neutralizing antibodies, alteration of cellular lymphocyte infiltration and prevention of pathogenesis
Summary
Virus replication initiates in epithelial cells and can establish latency in innervating sensory neurons. These viruses may reactivate periodically producing localized lesions in facial and genital epithelial tissues[1]. HSV can cause a spectrum of disease including but not limited to primary and recurrent infections of mucous membranes such as gingivostomatitis, herpes labialis, and genital infections. They can cause neonatal and congenital HSV infection, visceral HSV infections in immunocompromised hosts, and HSV encephalitis[6]. The major cause of infectious blindness in many developed countries is herpes infection and associated immunopathogenesis [11]
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