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‐α to augment the cellular immune response to DNA vaccination against HCV core protein. Three types of IFN‐α were investigated: the non‐species‐specific hybrid IFN A/D, human pegylated IFN‐α, and a plasmid that expressed murine IFN‐α. Low doses of hIFN‐A/D and hPegIFN‐α 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‐α 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. J. Med. Virol. 75:249–257, 2005. © 2004 Wiley‐Liss, Inc.