A glycoprotein H (gH)-deleted herpes simplex virus type 2 (HSV-2) was evaluated as a vaccine for the prevention of HSV-induced disease. This virus, which we term a DISC (disabled infectious single cycle) virus, can only complete one replication cycle in normal cells and should thus be safe yet still able to stimulate broad humoral and cell-mediated antiviral immune responses. A gH-deleted HSV-2 virus that has been tested as a vaccine in the guinea pig model of recurrent HSV-2 infection was constructed. Animals vaccinated with DISC HSV-2 showed complete protection against primary HSV-2-induced disease, even when challenged 6 months after vaccination. In addition, the animals were almost completely protected against recurrent disease. Even at low vaccination doses, there was a high degree of protection against primary disease. A reduction in recurrent disease symptoms was also observed following therapeutic vaccination of animals already infected with wild type HSV-2.

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 viruses, 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 vaccinated 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-induced 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.

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