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

Washington University School of Medicine, Department of Ophthalmology and Visual Sciences, Box 8096, 660 South Euclid, St Louis, MO 63110, USA 1 Author for correspondence: Patrick Stuart. Fax +1 314 362 6985. e-mail stuart{at}vision.wustl.edu 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.