A self-adjuvanting lipopeptide-based vaccine candidate for the treatment of hepatitis C virus infection.
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.
Chua
Brendon Y
BY
Department of Microbiology and Immunology, The University of Melbourne, Royal Parade, Parkville, Victoria 3010, Australia.
Eriksson
Emily M
EM
Brown
Lorena E
LE
Zeng
Weiguang
W
Gowans
Eric J
EJ
Torresi
Joseph
J
Jackson
David C
DC
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology; D015789:HLA-A2 Antigen / Q000235:genetics / Q000276:immunology; D006526:Hepatitis C / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D008074:Lipoproteins / Q000138:chemical synthesis / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D022223:Vaccines, Subunit / Q000276:immunology; D014761:Viral Hepatitis Vaccines / Q000276:immunology*
D015789:HLA-A2 Antigen; D008074:Lipoproteins; D022223:Vaccines, Subunit; D014761:Viral Hepatitis Vaccines; D018664:Interleukin-12; D007371:Interferon-gamma