Codelivery of PEG-IFN-alpha inhibits HCV DNA vaccine-induced T cell responses but not humoral responses in African green monkeys

Abstract

Although pegylated interferon alpha (PEG-IFN-α) with ribavirin treatment constitutes an effective means of treatment for chronic hepatitis C, novel approaches are needed due to the inefficient effects of the current therapy against chronic infection with genotype 1 virus. In this study, the immunomodulatory effects of PEG-IFN-α on multigenic HCV DNA vaccine-induced immunity were investigated in African green monkeys. Multigenic HCV DNA vaccination with and without PEG-IFN-α was safe and well tolerated, and induced significant long-term T cell and antibody responses. In addition, the induced immune responses were gradually increased by repeated injection. Interestingly, co-treatment with PEG-IFN-α significantly suppressed HCV DNA vaccine-induced T cell responses, but not antibody responses, which demonstrated that IFN-α could act as a negative regulator of T cell immune induction. However, the suppression of T cell responses by PEG-IFN-α could be overcome by two times more DNA vaccination, which suggests that combined therapy of DNA vaccine with PEG-IFN-α might be possible. Our results provide valuable information for the design of an effective therapeutic regimen to treat chronic HCV infection and to understand the immunomodulatory roles of PEG-IFN-α in immune induction by DNA vaccination.