The purpose of this research is to further our understanding of immunity to sexually transmitted herpes simplex virus type 2 (HSV-2). In women, HSV-2 infects the mucosa in the genital tract and spreads to the nervous system where it persists in sensory ganglia as latent virus. Under conditions of stress, latent virus is activated and causes recurrent disease. Development of a vaccine to prevent HSV-2 infections in the genital tract and subsequent latency is problematic because it requires sterile immunity, but factors that suppress reactivation of latent irus deserve thorough investigation. The only animal model for studies of recurrent herpetic disease in the genital tract uses the guinea pig, but this species is less suitable for immunologic studies than mice. We propose experiments to establish a mouse model for studies of genital recurrent herpetic disease. The aims of this proposal are: Specific Aim 1: Tod etermine whether treatment with acyclovir and/or passive transfer of polyclonal HSV-2 antibody or monoclonal antibody to HSV- 2 glycoprotein D to naive mice after intravaginal infection with HSV-2 will prevent or attenuate neurological disease; Specific Aim 2: To demonstrate latent virus in lumbosacral ganglia in mice that survive infection. Specific Aim 3: To determine whether latently infected mice show spontaneous and induce recurrent infection. Specific Aim 4: To test the hypothesis that therapeutic immunization of latently infected mice will reduce or eliminate recurrent infection and to compare the effectiveness of vaccines that stimulate humoral immunity alone or both humoral and T cell mediated immunity. If therapeutic immunization reduced recurrent infections in women, it would reduce severe herpes infections in newborns, decrease the sexually transmitted spread of this virus throughout the population, and improve women's reproductive health.