title: 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.
authors.affiliation: Department of Infectious Diseases, First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, The People's Republic of China.
authors.forename: Suna
authors.initials: S
authors.lastname: Wang
authors.forename: Qunying
authors.initials: Q
authors.lastname: Han
authors.forename: Guoyu
authors.initials: G
authors.lastname: Zhang
authors.forename: Ni
authors.initials: N
authors.lastname: Zhang
authors.forename: Zhu
authors.initials: Z
authors.lastname: Li
authors.forename: Jinghong
authors.initials: J
authors.lastname: Chen
authors.forename: Yi
authors.initials: Y
authors.lastname: Lv
authors.forename: Na
authors.initials: N
authors.lastname: Li
authors.forename: Fanfan
authors.initials: F
authors.lastname: Xing
authors.forename: Ningqiang
authors.initials: N
authors.lastname: Tian
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Zhu
authors.forename: Zhengwen
authors.initials: Z
authors.lastname: Liu
mesh_terms: D000276:Adjuvants, Immunologic / Q000009:adverse effects / Q000138:chemical synthesis / Q000494:pharmacology*; D000328:Adult; D051017:Apoptosis Regulatory Proteins / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology*; D018929:Cell Culture Techniques; D002470:Cell Survival / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000737:chemistry / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000737:chemistry; D005260:Female; D056945:Hep G2 Cells; D006514:Hepatitis B Surface Antigens / Q000737:chemistry*; D019694:Hepatitis B, Chronic / Q000097:blood / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D015847:Interleukin-4 / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009838:Oligodeoxyribonucleotides; D010446:Peptide Fragments / Q000737:chemistry*; D011993:Recombinant Fusion Proteins / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology*; D000077022:Survivin; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology; D055815:Young Adult; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000276:Adjuvants, Immunologic; D051017:Apoptosis Regulatory Proteins; C423449:CpG ODN 1826; D000939:Epitopes; C512124:HIV-TAT-survivin (T34A) protein; D006514:Hepatitis B Surface Antigens; D009838:Oligodeoxyribonucleotides; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D000077022:Survivin; D054322:tat Gene Products, Human Immunodeficiency Virus; D015847:Interleukin-4; D007371:Interferon-gamma; D004247:DNA