Therapeutic periocular vaccination with a subunit vaccine induces higher levels of herpes simplex virus-specific tear secretory immunoglobulin A thansystemic vaccination and provides protection against recurrent spontaneousocular shedding of virus in latently infected rabbits

Rabbits latently infected with herpes simplex virus type 1 (HSV-1) were vac cinated either periocularly or systemically with a subunit vaccine (gB2 + g D2) plus adjuvant or adjuvant alone. Tear films were collected daily to mea sure recurrent infectious HSV-1 shedding. After systemic vaccination, the l atently infected rabbits were not protected against recurrent ocular viral shedding (HSV-1-positive tear film cultures/total cultures) compared with e ither the systemic or periocular adjuvant controls (systemic vaccination = 49 of 972, 5.0%; systemic control = 46 of 972, 4.7%; periocular control = 4 3 of 930, 4.6%; P > 0.8). In contrast, latently infected rabbits vaccinated periocularly with the same vaccine had significantly reduced recurrent she dding (20 of 1026, 2.0%) compared with controls (P < 0.001) or systemic vac cination (P = 0.0002). Thus, recurrent HSV-1 shedding was significantly red uced by therapeutic local periocular subunit vaccination but not by therape utic systemic subunit vaccination. Neutralizing antibody titers in the seru m of systemically and ocularly vaccinated rabbits was similar. In contrast, HSV-specific tear secretory immunoglobulin A was significantly higher in t he ocularly vaccinated group (P < 0.01). These results strongly suggest tha t in the rabbit, and presumably in humans, the local ocular (mucosal) immun e response is much more important than the systemic immune response for the rapeutic protection against recurrent ocular HSV-1. Thus development of a t herapeutic vaccine against recurrent ocular HSV-1 should be directed at enh ancing the local ocular (mucosal) immune response. (C) 1998 Academic Press.