Document Detail


A self-adjuvanting lipopeptide-based vaccine candidate for the treatment of hepatitis C virus infection.
MedLine Citation:
PMID:  18455278     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Effective CD8(+) T cell responses have been induced using totally synthetic self-adjuvanting lipopeptides containing the dipalmitoyl-S-glyceryl cysteine lipid moiety, which is a ligand for Toll-like receptor 2 (TLR2) on dendritic cells (DC). In this study, we evaluated the use of lipopeptide vaccine candidates containing HLA-A2-restricted epitopes for DC-based immunotherapy of HCV infection. Lipopeptides were able to induce specific CD8(+) T cell responses in HLA-A2 transgenic mice and consistently activated human monocyte-derived DC from both healthy individuals and HCV infected patients. Lipopeptide-pulsed human DC were also found to secrete the pro-inflammatory cytokine IL-12p70 and were able to activate antigen-specific IFN-gamma production by autologous CD8(+) T cells obtained from a hepatitis C patient. These results show that DC from HCV patients can be matured and antigen loaded with TLR2-targeting lipopeptides for effective presentation of CD8(+) T cell epitopes; the use of autologous lipopeptide-pulsed DC or direct lipopeptide vaccination may be successful approaches for the priming or boosting of anti-HCV CD8(+) T cell responses to aid in the clearance of the virus in chronically infected individuals.
Authors:
Brendon Y Chua; Emily M Eriksson; Lorena E Brown; Weiguang Zeng; Eric J Gowans; Joseph Torresi; David C Jackson
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-04-07
Journal Detail:
Title:  Vaccine     Volume:  26     ISSN:  0264-410X     ISO Abbreviation:  Vaccine     Publication Date:  2008 Sep 
Date Detail:
Created Date:  2008-08-25     Completed Date:  2008-10-15     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  8406899     Medline TA:  Vaccine     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  4866-75     Citation Subset:  IM    
Affiliation:
Department of Microbiology and Immunology, The University of Melbourne, Royal Parade, Parkville, Victoria 3010, Australia.
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MeSH Terms
Descriptor/Qualifier:
Animals
CD8-Positive T-Lymphocytes / immunology
Cells, Cultured
Dendritic Cells / immunology
HLA-A2 Antigen / genetics,  immunology
Hepatitis C / immunology*
Humans
Interferon-gamma / secretion
Interleukin-12 / secretion
Lipoproteins / chemical synthesis,  immunology*
Mice
Mice, Inbred C57BL
Mice, Transgenic
Vaccines, Subunit / immunology
Viral Hepatitis Vaccines / immunology*
Chemical
Reg. No./Substance:
0/HLA-A2 Antigen; 0/Lipoproteins; 0/Vaccines, Subunit; 0/Viral Hepatitis Vaccines; 187348-17-0/Interleukin-12; 82115-62-6/Interferon-gamma

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