Augmentation of Natural Immune Defence Mechanisms and Therapeutic Potential of a Mismatched Double-stranded Polynucleotide in Cutaneous Herpes Simplex Virus Type 2 Infection

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Abstract
We studied the effect of an analogue of polyinosinic acid:polycytidylic acid, the mismatched poly(rI) .cntdot. 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 .mu.g/g body weight, five doses at 48 h intervals) of poly(rI) .cntdot. poly(rC12U) during initial HSV-2 infection caused a significant (P < 0.05) reduction in virus titres in the skin and decreased (P < 0.01) the duration and severity of the primary cutaneous lesions. The incidence and frequency of subsequent recurrent episodes were also significantly (P < 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) .cntdot. 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) .cntdot. poly(rC12U) or IFN.