Immunostimulatory effects of three classes of CpG oligodeoxynucleotides on PBMC from HCV chronic carriers

Curtis L Cooper¹ , Navneet K Ahluwalia² , Susan M Efler² , Jörg Vollmer³ , Arthur M Krieg⁴ and Heather L Davis²

¹Division of Infectious Diseases, University of Ottawa at The Ottawa Hospital and Ottawa Health Research Institute, Ottawa, Canada

²Coley Pharmaceutical Canada, Ottawa, Canada

³Coley Pharmaceutical GmbH, Langenfeld, Germany

⁴Coley Pharmaceutical Group, Wellesley MA, USA

author email corresponding author email

Journal of Immune Based Therapies and Vaccines 2008, 6:3doi:10.1186/1476-8518-6-3


Published:	9 June 2008

Abstract

Background

Chronic hepatitis C virus (HCV) infection results from weak or absent T cell responses. Pegylated-interferon-alpha (IFN-α) and ribavirin, the standard of care for chronic HCV, have numerous immune effects but are not potent T cell activators. A potent immune activator such as TLR9 agonist CpG oligodeoxynucleotide (CpG) may complement current treatment approaches.

Methods

Peripheral blood mononuclear cells (PBMC) obtained from HCV chronic carriers who failed previous treatment and from healthy donors were incubated in vitro with the three main CpG classes (A, B or C), recombinant IFN-α-2b (IntronA) and/or ribavirin. Proliferation and cytokine secretion (IFN-α, IL-10 and IP-10) were evaluated.

Results

CpG induced proliferation and cytokine secretion in patterns expected for each CpG class with similar group means for HCV and healthy donors. IntronA and ribavirin, alone or together, had no detectable effects. IntronA and C-Class CpG together induced more IFN-α than CpG alone in most subjects. IFN-α secretion was proportional to the number of plasmacytoid dendritic cells in PBMC from healthy donors but not HCV donors in whom responses were highly heterogeneous.

Conclusion

The strong immune stimulatory effect of CpG on PBMC isolated from treatment-failed HCV patients suggests possible utility alone or in combination with current HCV antiviral treatment.