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

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Although pegylated interferon alpha (PEG-IFN-alpha) 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-alpha on multigenic HCV DNA vaccine-induced immunity were investigated in African green monkeys. Multigenic HCV DNA vaccination with and without PEG-IFN-alpha 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-alpha significantly suppressed HCV DNA vaccine-induced T cell responses, but not antibody responses, which demonstrated that IFN-alpha could act as a negative regulator of T cell immune induction. However, the suppression of T cell responses by PEG-IFN-alpha could be overcome by two times more DNA vaccination, which suggests that combined therapy of DNA vaccine with PEG-IFN-alpha 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-alpha in immune induction by DNA vaccination.
Publisher
ELSEVIER SCI LTD
Issue Date
2008-07
Language
English
Article Type
Article
Keywords

HEPATITIS-C-VIRUS; INTERFERON-ALPHA; DIFFERENTIAL REGULATION; POWERFUL ADJUVANT; GENE-EXPRESSION; DENDRITIC CELLS; IMMUNE-RESPONSE; I INTERFERON; BETA; INFECTION

Citation

VACCINE, v.26, no.32, pp.3978 - 3983

ISSN
0264-410X
DOI
10.1016/j.vaccine.2008.05.017
URI
http://hdl.handle.net/10203/198327
Appears in Collection
MSE-Journal Papers(저널논문)
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