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HBsAg 融合蛋白和初免-加强免疫增强 HCV 多表位 DNA 疫苗诱导的 Th1 和 CTL 应答

Fusion of HBsAg and prime/boosting augment Th1 and CTL responses to HCV polytope DNA vaccine.

机构信息

Hepatitis & AIDS Department-NRGB Laboratory, Pasteur institute of Iran, Tehran, Iran.

出版信息

Cell Immunol. 2010;261(2):93-8. doi: 10.1016/j.cellimm.2009.11.005. Epub 2010 Jan 6.

Abstract

Correlation of hepatitis C virus (HCV) spontaneous resolution with Th1 and CD8(+)CTL responses during natural infection implies the potentiality of poly-CTL-epitopic HCV vaccines. We recently reported in silico design and construction of DNA vaccines (pcPOL-plasmids) harboring HCV CTL epitopes. Herein, we provide data of mice immunization by pcPOL, (encoding; core(132-142) [C], E2(405-414) [E(4)], E2(614-622) [E(6)] and NS3(1406-1415) [N] CD8(+)CTL epitopes as CE(4)E(6)N polytope) and its HBsAg-fused counterpart (pcHPOL), compared to the adjuvant-formulated (Montanide+CpG) CE(4)E(6)N synthetic-peptide immunization. All vaccinated groups developed different levels of cellular responses, however, only the pcHPOL-immunized mice elicited strong CTLs and IFN-gamma-secreting cells that were further augmented towards a Th1 response and partial tumor protection by DNA-prime/peptide-boosting regimen. Priming with HBsAg alone could not afford its augmenting effect indicating the importance of priming by polytope itself. Hence, fusion of immunocarriers like HBsAg conjoined with DNA-prime/peptide-boost immunization regimen seems a strategy to enhance the epitope-specific immune responses towards poly-CTL-epitopic vaccines.

摘要

丙型肝炎病毒(HCV)自然感染中自发清除与 Th1 和 CD8(+)CTL 反应的相关性表明多 CTL 表位 HCV 疫苗具有潜力。我们最近报道了含有 HCV CTL 表位的 DNA 疫苗(pcPOL-质粒)的计算机设计和构建。在此,我们提供了用 pcPOL 免疫小鼠的数据,(编码;核心(132-142)[C]、E2(405-414)[E(4)]、E2(614-622)[E(6)]和 NS3(1406-1415)[N]CD8(+)CTL 表位作为 CE(4)E(6)N 多表位)及其 HBsAg 融合对应物(pcHPOL),与佐剂配方(Montanide+CpG)CE(4)E(6)N 合成肽免疫相比。所有接种组均产生不同水平的细胞反应,但只有 pcHPOL 免疫的小鼠诱导出强烈的 CTL 和 IFN-γ分泌细胞,进一步增强了 Th1 反应和部分肿瘤保护,通过 DNA 初免/肽增强方案。单独用 HBsAg 进行初免不能提供其增强作用,表明多表位本身初免的重要性。因此,将免疫载体如 HBsAg 与 DNA 初免/肽增强免疫方案融合,似乎是增强多 CTL 表位疫苗的表位特异性免疫反应的一种策略。

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