VACCINE THERAPY FOR OCULAR HERPES-SIMPLEX VIRUS (HSV) INFECTION - PERIOCULAR VACCINATION REDUCES SPONTANEOUS OCULAR HSV TYPE-1 SHEDDING IN LATENTLY INFECTED-RABBITS

Periocular vaccination of rabbits with preexisting herpes simplex viru s type 1 (HSV-1) latent infection with recombinant HSV-2 glycoproteins B and D (gB2 and gD2) plus adjuvant significantly reduced ocular vira l shedding. Rabbits were infected in both eyes with HSV-1 strain McKra e. Following HSV-1 infection and the establishment of latency (28 days postinfection), rabbits were given a periocular subconjunctival vacci nation three times at 3-week intervals. Beginning 3 weeks after the fi nal vaccination, tear films were collected daily and cultured to detec t the presence of HSV-1 and determine the spontaneous HSV-1 ocular she dding rates. Periocular vaccination increased the mean HSV-1 serum neu tralizing antibody titer to fivefold above that seen in mock-vaccinate d latently infected rabbits. gB enzyme-linked immunosorbent assay (ELI SA) antibody titers were increased approximately 8-fold, and gD ELISA antibody titers were increased 60-fold. These increases were all stati stically significant (P < 0.0001). In two independent experiments, vac cination reduced the spontaneous shedding rate by approximately 2.5-fo ld (P < 0.0004). In addition, the percentage of eyes that never shed v irus during the 6 week postvaccination test period increased threefold (20% in controls versus 60% in vaccinated animals; P < 0.007). These results show that spontaneous ocular shedding of HSV-1 in latently inf ected rabbits can be significantly reduced by local periocular vaccina tion. This is the first report in any animal model of a successful the rapeutic vaccine against recurrent HSV-1 ocular shedding. These result s support the concept that development of a therapeutic vaccine for oc ular HSV-1 recurrence in humans is possible.