THERAPEUTIC VACCINE THAT REDUCES RECURRENT HERPES-SIMPLEX VIRUS TYPE-1 CORNEAL DISEASE

PURPOSE. To investigate the therapeutic efficacy of periocular vaccina tion with herpes simplex virus (HSV) recombinant glycoprotein D from H SV-1 (gD1) or HSV-2 (gD2) in decreasing HSV-induced recurrent dendriti c keratitis and HSV-induced recurrent ocular shedding in rabbits laten tly infected with HSV-1. METHODS. Rabbits latently infected with HSV-1 were vaccinated periocularly (by subconjunctival injection) with gD1 and adjuvant, gD2 and adjuvant, or adjuvant alone. Eyes were examined daily for 49 days for recurrent herpetic keratitis and for recurrent i nfectious HSV-1 shedding. RESULTS. In both vaccinated groups, a signif icantly decreased number of eyes exhibited recurrences of herpetic ker atitis compared with recurrences in adjuvant-treated control eyes (gD1 group, 27/1372, [2%]; gD2 group, 24/1274, [2%]; and control, 54/1274 [4%]; P < 0.005). Eyes in the gD1-vaccinated group (44/1308 [3.4%]; P = 0.01), but not those in the gD2-vaccinated group (71/1274 [5.6%]; P = 0.93), had significantly decreased viral shedding (positive cultures compared with total cultures) compared with eyes in the adjuvant-trea ted control group (69 of 1275 [5.4%]). CONCLUSIONS. Recurrent HSV-1 co rneal disease was significantly reduced by therapeutic local periocula r vaccination. The vaccine may be more efficacious against HSV-1-induc ed recurrent corneal disease than against recurrent HSV-1 ocular shedd ing. Its efficacy against corneal disease appeared to be longer lastin g than its efficacy against recurrent spontaneous shedding. The heteto typic gD2 vaccine was as efficacious as the homotypic gD1 vaccine agai nst recurrent corneal disease, whereas the homotypic vaccine was much more efficacious than the heterotypic vaccine against recurrent HSV-1 shedding. This is the first report in any animal model of a successful therapeutic vaccine against recurrent HSV-1-induced corneal disease. These results support the concept that development of a therapeutic va ccine for ocular HSV-1 recurrence in humans may be possible.