Vaccination with ubiquitin-hepatitis B core antigen-cytoplasmic transduction peptide enhances the hepatitis B virus-specific cytotoxic T-lymphocyte immune response and inhibits hepatitis B virus replication in transgenic mice.
Vaccination with ubiquitin-hepatitis B core antigen-cytoplasmic transduction peptide enhances the hepatitis B virus-specific cytotoxic T-lymphocyte immune response and inhibits hepatitis B virus replication in transgenic mice.
复制标题
接种泛素-乙型肝炎核心抗原-细胞质转导肽可增强转基因小鼠体内乙型肝炎病毒特异性细胞毒性T淋巴细胞免疫反应并抑制乙型肝炎病毒复制。
DOI：
10.3892/mmr.2015.3834
复制
发表时间：
2015
影响因子：
3.4
通讯作者：
Zheng
中科院分区：
文献类型：
--
作者：
M. Zhuo;Linlin Song;Yuyan Tang;Shenglan Dai;Xiaohua Chen;Yong;G. Zang;Zheng
慢性乙型肝炎病毒 (HBV) 感染的特点是 1 型 T 辅助细胞 (Thl) 免疫功能受损和 HBV 特异性 T 细胞反应较差。泛素 (Ub) 是一种高度保守的小调节蛋白，通常作为靶蛋白的信号，在蛋白酶体中被识别和降解。 Ub 介导的抗原的快速降解可有效刺激细胞介导的免疫反应。因此，Ub-HBV核心抗原（HBcAg）-细胞质转导肽（CTP）融合蛋白被设计用于将外来修饰抗原特异性递送至抗原呈递细胞的细胞质。使用 HBV 转基因小鼠来确定 Ub-HBcAg-CTP 是否会恢复这些动物的 HBV 特异性免疫反应和抗病毒免疫力。结果表明，与 HBcAg-CTP、IFN-α、Ub-HBcAg、HBcAg 和磷酸盐缓冲盐水组相比，合成的 Ub-HBcAg-CTP 不仅显着提高了白细胞介素 2 和干扰素 (IFN)-γ 的水平，而且还诱导了最高的 IFN-γ+ CD8+ T 细胞数量和 HBV 特异性细胞毒性 T 淋巴细胞 (CTL) 反应，表明有很强的免疫反应。此外，融合蛋白引起的特异性CTL活性的增强降低了乙型肝炎表面抗原（HBsAg）和HBV DNA血清水平，并减少了HBV转基因小鼠肝组织中HBsAg和HBcAg的表达，表明具有治疗作用。总之，本研究提供的证据表明，Ub-HBcAg-CTP 可激活 Th1 依赖性免疫，触发功能性 T 细胞反应，并随后抑制 HBV 转基因小鼠中的病毒复制。这些观察结果表明，融合蛋白可能代表慢性和持续性乙型肝炎主动免疫治疗的创新和有前途的候选者。
Chronic hepatitis B virus (HBV) infection is characterized by functionally impaired type 1 T-helper cell (Thl) immunity and poor HBV‑specific T‑cell responses. Ubiquitin (Ub), a highly conserved small regulatory protein, commonly serves as a signal for target proteins that are recognized and degraded in proteasomes. The rapid degradation of Ub‑mediated antigens results in efficient stimulation of cell‑mediated immune responses. Thus, the Ub‑HBV core antigen (HBcAg)‑cytoplasmic transduction peptide (CTP) fusion protein was designed for specific delivery of a foreign modified antigen to the cytoplasm of antigen‑presenting cells. HBV transgenic mice were used to determine whether Ub‑HBcAg‑CTP would restore HBV‑specific immune responses and anti‑viral immunity in these animals. The results demonstrated that synthesized Ub‑HBcAg‑CTP not only significantly increased the levels of interleukin‑2 and interferon (IFN)‑γ compared with those in the HBcAg‑CTP, IFN‑α, Ub‑HBcAg, HBcAg and phosphate‑buffered saline groups, but additionally induced the highest IFN‑γ+ CD8+ T‑cell numbers and HBV‑specific cytotoxic T lymphocyte (CTL) responses, indicating a strong immune response. In addition, enhancement of specific CTL activity provoked by the fusion protein reduced hepatitis B surface antigen (HBsAg) and HBV DNA serum levels and diminished the expression of HBsAg and HBcAg in liver tissue of HBV transgenic mice, suggesting that there was a therapeutic effect. In conclusion, the present study provided evidence that Ub‑HBcAg‑CTP activated the Th1‑dependent immunity, triggered functional T cell responses and subsequently inhibited viral replication in HBV transgenic mice. These observations suggested that the fusion protein may represent an innovative and promising candidate for active immunotherapy during chronic and persistent HBV.
影响因子：
15.9
作者：
Boni, C;Bertoletti, A;Ferrari, C
通讯作者：
Ferrari, C