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.
Keadle
Tammie L
TL
Washington University School of Medicine, Department of Ophthalmology and Visual Sciences, Box 8096, 660 South Euclid, St Louis, MO 63110, USA1.
Laycock
Keith A
KA
Washington University School of Medicine, Department of Ophthalmology and Visual Sciences, Box 8096, 660 South Euclid, St Louis, MO 63110, USA1.
Morris
Jessica L
JL
Washington University School of Medicine, Department of Ophthalmology and Visual Sciences, Box 8096, 660 South Euclid, St Louis, MO 63110, USA1.
Leib
David A
DA
Washington University School of Medicine, Department of Ophthalmology and Visual Sciences, Box 8096, 660 South Euclid, St Louis, MO 63110, USA1.
Morrison
Lynda A
LA
Washington University School of Medicine, Department of Ophthalmology and Visual Sciences, Box 8096, 660 South Euclid, St Louis, MO 63110, USA1.
Pepose
Jay S
JS
Washington University School of Medicine, Department of Ophthalmology and Visual Sciences, Box 8096, 660 South Euclid, St Louis, MO 63110, USA1.
Stuart
Patrick M
PM
Washington University School of Medicine, Department of Ophthalmology and Visual Sciences, Box 8096, 660 South Euclid, St Louis, MO 63110, USA1.
D000818:Animals; D002522:Chlorocebus aethiops; D003318:Corneal Opacity / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D004195:Disease Models, Animal; D022301:Herpes Simplex Virus Vaccines / Q000276:immunology / Q000627:therapeutic use*; D018259:Herpesvirus 1, Human / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D016849:Keratitis, Herpetic / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D051379:Mice; D012260:Ribonucleases; D014611:Vaccination; D014709:Vero Cells; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology*
D022301:Herpes Simplex Virus Vaccines; D014764:Viral Proteins; C070722:virion host shutoff protein, Simplexvirus; D012260:Ribonucleases