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.
Int Immunopharmacol. 2011 Apr;11(4):406-11. doi: 10.1016/j.intimp.2010.12.005. Epub 2010 Dec 21.
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.
该融合肽由乙型肝炎核心抗原(HBcAg)(18-27)CTL 表位和人类免疫缺陷病毒(HIV)-Tat(49-57)肽组成,当与 CpG 寡脱氧核苷酸(CpG ODN)佐剂联合使用时,在免疫耐受期慢性乙型肝炎病毒(HBV)感染患者的 PBMC 中评估其活性。结果表明,与融合肽或 CpG ODN 单独使用相比,CpG ODN 佐剂的融合肽可诱导 PBMC 中 IFN-γ 和 IL-4 水平显著升高。融合肽加 CpG ODN 对 IFN-γ 的增强幅度远高于对 IL-4 的增强幅度。细胞毒性测定表明,在大多数检测的 E/T 比值下,融合肽加 CpG ODN 刺激的效应细胞对靶细胞的裂解百分比高于融合肽或 CpG ODN 单独使用时的百分比。融合肽加 CpG ODN 对 IFN-γ 的增强幅度也远高于对靶细胞裂解百分比的增强幅度。结论:CpG ODN 佐剂的 HBcAg(18-27)和 HIV-Tat(49-57)融合肽可能具有更高的诱导 IFN-γ 的能力,而不是诱导 IL-4 和细胞毒性的能力,这表明 IFN-γ 介导的非细胞溶解性病毒失活具有有利的免疫反应,并有潜力打破慢性 HBV 感染中的耐受状态。