Therapeutic vaccination with vhs^- herpes simplex virus reduces the severity of recurrent herpetic stromal keratitis in mice

Virion host shutoff (vhs)-deficient herpes simplex virus (HSV) was tested as a therapeutic vaccine in a mouse model of UV light-induced recurrent herpetic stromal keratitis. Four weeks after primary corneal infection, mice were vaccinated intraperitoneally with vhs^- vaccine or control. Four weeks after vaccination, the eyes of latently infected mice were UV-B irradiated to induce recurrent virus shedding and disease. Post-irradiation corneal opacity in latently infected, vhs^--vaccinated mice was significantly reduced compared to control-vaccinated mice (P = 0.007 to 0.035). The incidence and duration of recurrent virus shedding were the same in both groups. Antibody titres were increased (P = 0.05) and delayed type hypersensitive responses were unaffected by vhs^- vaccination. Combined with studies using different vaccination timing and vhs^- genotypes, these data suggest that deletion of vhs is a useful strategy in the development of a therapeutic HSV vaccine, and that temporal and genetic factors influence vaccination outcome.