Augmentation of natural immune defence mechanisms and therapeutic potential of a mismatched double-stranded polynucleotide in cutaneous herpes simplex virus type 2 infection.

We studied the effect of an analogue of polyinosinic acid:polycytidylic acid, the mismatched poly(rI).poly(rC12U), on herpes simplex virus type 2 (HSV-2)-induced cutaneous disease in the guinea-pig. Recurrence patterns and HSV-2-induced immune responses were also defined. Intranasal administration (1.5 micrograms/g body weight, five doses at 48 h intervals) of poly(rI).poly(rC12U) during initial HSV-2 infection caused a significant (P less than 0.05) reduction in virus titres in the skin and decreased (P less than 0.01) the duration and severity of the primary cutaneous lesions. The incidence and frequency of subsequent recurrent episodes were also significantly (P less than 0.01) reduced. Titres of serum neutralizing antibody were identical in treated and untreated animals. Interferon (IFN) activity was detectable in the sera from poly(rI).poly(rC12U)-treated animals. Peripheral blood mononuclear (PBL) and spleen cells from treated animals had enhanced cytotoxic activity for HSV-2-infected and uninfected target cells. The cytotoxic activity of the PBL was enhanced by treatment in vitro with poly(rI).poly(rC12U) or IFN.