ABSTRACT
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.
Subject(s)
Herpes Genitalis/prevention & control , Herpesvirus 2, Human/immunology , Vaccines, Synthetic , Viral Vaccines , Animals , Antibodies, Viral/blood , Chlorocebus aethiops , Female , Gene Deletion , Genes, Viral , Guinea Pigs , Herpes Genitalis/therapy , Herpesvirus 2, Human/genetics , Herpesvirus 2, Human/physiology , Immunization Schedule , Recurrence , Transfection , Vaccination , Vaccines, Inactivated/administration & dosage , Vaccines, Inactivated/immunology , Vaccines, Inactivated/therapeutic use , Vaccines, Synthetic/administration & dosage , Vaccines, Synthetic/immunology , Vero Cells , Viral Envelope Proteins/genetics , Viral Vaccines/administration & dosage , Viral Vaccines/immunology , Viral Vaccines/therapeutic use , Virus ReplicationABSTRACT
The vaccine potential of a genetically disabled Herpes Simplex Virus Type 1 virus (DISC HSV-1) was investigated in the guinea pig model of intravaginal (i.vag.) HSV-2 infection. Three mucosal vaccination routes, i.vag., intranasal (i.n.) and oral, were compared for their ability to protect guinea pigs from challenge with wild-type HSV-2. Each was effective, particularly the i.n. route, which almost completely abolished primary disease. This was accompanied by significantly lower challenge virus titres in vaginal swabs collected from the vaccinated animals. In all cases, vaccination with the inactivated virus preparation provided substantially less protection from disease than the live DISC HSV-1 by the equivalent route. Antibody levels in serum and vaginal washes were measured both after vaccination and challenge by ELISA and neutralization tests. The highest titres were observed following administration of the DISC HSV-1 vaccine by the i.n. route. Significant increases in IgA and IgG in vaginal wash fluids were also found in these vaccinated animals.
