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

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 immunomo...

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Bibliographic Details
Published in:Vaccine 2008-07, Vol.26 (32), p.3978-3983
Main Authors: PARK, Su-Hyung, SANG RAE LEE, BYUNG HWA HYUN, KIM, Byong-Moon, YOUNG CHUL SUNG
Format: Article
Language:English
Subjects:
Applied microbiology
Biological and medical sciences
Blood
Deoxyribonucleic acid
DNA
Fundamental and applied biological sciences. Psychology
Gene expression
Hematology
Hepatitis
Immune system
Infections
Lymphocytes
Microbiology
Miscellaneous
Peptides
Studies
Vaccines
Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects)
Virology
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Summary: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.
ISSN:0264-410X
1873-2518
DOI:10.1016/j.vaccine.2008.05.017