Abstract
Eradication of chronic hepatitis C virus (HCV) infection depends upon a broad-based cellular immune response. Genetic immunization stimulates such a response, but the resultant activity is generally weak. Type 1 interferons (IFNs), which are known for their direct anti-viral and anti-proliferative properties, possess vigorous immunomodulatory properties. The aim of this study was to assess the capacity of IFN-alpha to augment the cellular immune response to DNA vaccination against HCV core protein. Three types of IFN-alpha were investigated: the non-species-specific hybrid IFN A/D, human pegylated IFN-alpha, and a plasmid that expressed murine IFN-alpha. Low doses of hIFN-A/D and hPegIFN-alpha augmented three to fourfold the cellular immune response to DNA-based vaccination, determined in conventional CTL assays, as well as in an in vivo tumor challenge model. Importantly, augmentation occurred within a narrow concentration range; a further increase in IFN dosage suppressed the CTL response significantly. Humoral immunity showed a very similar pattern of augmentation. These findings demonstrate that the immunomodulatory properties of IFN-alpha can be exploited to augment DNA based immunization, but it is important to consider the effects of dose on both cellular and humoral immune response for optimal augmentation.
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