CpG oligodeoxynucleotide-adjuvanted fusion peptide derived from HBcAg epitope and HIV-Tat may elicit favorable immune response in PBMCs from patients with chronic HBV infection in the immunotolerant phase

Abstract

The absence or insufficiency of specific immune response results in chronic hepatitis B virus (HBV) infection and immunotolerance. Therapeutic fusion peptide containing hepatitis B core antigen (HBcAg) 18–27 CTL epitope and human immunodeficiency virus (HIV)-Tat 49–57 peptide was synthesized and the activity when adjuvanted with CpG oligodeoxynucleotide (CpG ODN) was evaluated in PBMCs from patients with chronic HBV infection in the immunotolerant phase in this study. Results showed that the fusion peptide when adjuvanted with CpG ODN could induce significantly higher levels of IFN-γ and IL-4 in the PBMCs compared with fusion peptide or CpG ODN alone. The magnitude of augmentation to IFN-γ by the fusion peptide plus CpG ODN was much higher than that to IL-4. Cytotoxicity assay showed that the percentage of target cell lysis by effector cells stimulated by fusion peptide plus CpG ODN was higher than that in fusion peptide or CpG ODN alone at most of the E/T ratios tested. The magnitude augmented to IFN-γ by fusion peptide plus CpG ODN was also much higher than that to the percentage of target cell lysis. It is concluded that HBcAg 18–27 and HIV-Tat 49–57 fusion peptide when adjuvanted with CpG ODN may have much higher potency to induce IFN-γ than to induce IL-4 and cytotoxicity, suggesting the favorable immune response towards noncytolytic inactivation of the virus mediated by IFN-γ and the potential to break the tolerant state in chronic HBV infection.