LIPOSOME-FORMULATED INTERLEUKIN-2 AS AN ADJUVANT OF RECOMBINANT HSV GLYCOPROTEIN GD FOR THE TREATMENT OF RECURRENT GENITAL HSV-2 IN GUINEA-PIGS

The use of interleukin-2 (IL-2) as an adjuvant to enhance an antigen-induced immunotherapeutic effect was investigated using guinea-pigs with established HSV-2 infection. Animals treated with four weekly doses of liposome-formulated IL-2 (2.7 x 10(5) U kg-1 dose) overlapping two biweekly doses of an HSV-recombinant glycoprotein D (rgD) treatment demonstrated almost-equal-to 70% reduction in HSV-2 recurrent disease compared with placebo (p < 0.005). Combination therapy rgD plus liposome-formulated IL-2 exhibited almost-equal-to 30% greater therapeutic effect than either agent alone (p < 0.05). Liposome formulation of IL-2 was essential to elicit the adjuvant effect. Identical biweekly dosing or more frequent daily dosing of soluble IL-2 did not produce additional therapeutic effects, suggesting the role of liposome targeting to lymph nodes. Although rgD plus liposome-formulated IL-2 induced a marginal early antibody response to rgD, there was no significant increase in overall antibody response. Combination therapy increased the frequency of minimally positive HSV lymphoproliferative response.