lIDO Protective Vaccination against Primary and Recurrent Disease Caused by Herpes Simplex Virus (HSV) Type 2 Using a Genetically Disabled HSV-l

The vaccine potential of a mutant herpes simplex virus (HSV) type 1, with a deletion in the glycoprotein H (gH) gene, was evaluated. The virus requires a gH-expressing cell line for multi-cycle growth but can complete a single cycle of infection in noncomplementing cells. Such vi-ruses, termed DISC (disabled infectious single cycle) viruses, should be safe, yet still able to stimulate humoral and cell-mediated responses against a broad range of virus antigens in vacci-nated hosts. Prophylactic vaccination of guinea pigs with DISC HSV-1, by ear scarification or direct infection of the vaginal mucosa, afforded a high degree of protection against HSV-2-in-duced primary genital disease and reduced significantly the frequency of subsequent disease recurrence. There was also a trend toward reduced recurrence following therapeutic vaccination of animals already infected with HSV-2. DISC HSV vaccination, therefore, offers an effective route for control of HSV disease. We recently began to explore a new approach for develop-ment of safe and broadly effective virus vaccines based on the creation ofgenetically modified viruses that we call DISC (disabled infectious single-cycle) viruses. In these viruses a