Publications & Reports

A self-adjuvanting lipopeptide-based vaccine candidate for the treatment of hepatitis C virus infection.

Chua BY, Eriksson EM, Brown LE, Zeng WG, Gowans EJ, Torresi J, Jackson DC
Department of Microbiology and Immunology, The University of Melbourne, Royal Parade, Parkville, Victoria 3010, Australia.

Abstract

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.

Publication

  • Journal: Vaccine
  • Published: 02/09/2008
  • Volume: 26
  • Issue: 37
  • Pagination: 4866-4875

Author

Health Issue