Document Detail


Type 1 interferon augments DNA-based vaccination against hepatitis C virus core protein.
MedLine Citation:
PMID:  15602727     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Stephan Gehring; Stephen H Gregory; Noriyoshi Kuzushita; Jack R Wands
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of medical virology     Volume:  75     ISSN:  0146-6615     ISO Abbreviation:  J. Med. Virol.     Publication Date:  2005 Feb 
Date Detail:
Created Date:  2004-12-21     Completed Date:  2005-01-31     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  7705876     Medline TA:  J Med Virol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  249-57     Citation Subset:  IM    
Affiliation:
The Liver Research Center, Rhode Island Hospital and Brown Medical School, Providence, Rhode Island 02903, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
CD8-Positive T-Lymphocytes / immunology
Cytotoxicity, Immunologic
Female
Hepatitis C / immunology*
Interferon Alfa-2a / administration & dosage,  immunology*
Interferon Type I, Recombinant / administration & dosage,  immunology*
Killer Cells, Natural / immunology
Mice
Mice, Inbred BALB C
Polyethylene Glycols / administration & dosage
T-Lymphocytes, Cytotoxic / immunology
Time Factors
Vaccines, DNA / immunology
Viral Core Proteins / immunology*
Viral Hepatitis Vaccines / administration & dosage,  immunology*
Grant Support
ID/Acronym/Agency:
AA-20169/AA/NIAAA NIH HHS; AA-20666/AA/NIAAA NIH HHS; CA-35711/CA/NCI NIH HHS; P20RR 15578/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
0/Interferon Type I, Recombinant; 0/Polyethylene Glycols; 0/Vaccines, DNA; 0/Viral Core Proteins; 0/Viral Hepatitis Vaccines; 0/peginterferon alfa-2a; 76543-88-9/Interferon Alfa-2a

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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