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首页> 外文期刊>The Journal of Immunology: Official Journal of the American Association of Immunologists >Enhanced and sustained CD8+ T cell responses with an adenoviral vector-based hepatitis C virus vaccine encoding NS3 linked to the MHC class II chaperone protein invariant chain.
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Enhanced and sustained CD8+ T cell responses with an adenoviral vector-based hepatitis C virus vaccine encoding NS3 linked to the MHC class II chaperone protein invariant chain.

机译:用基于腺病毒载体的丙型肝炎丙型肝炎病毒疫苗增强和持续的CD8 + T细胞应答,该疫苗编码与MHC II类伴侣蛋白不变链相连的NS3。

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摘要

Potent and broad cellular immune responses against the nonstructural (NS) proteins of hepatitis C virus (HCV) are associated with spontaneous viral clearance. In this study, we have improved the immunogenicity of an adenovirus (Ad)-based HCV vaccine by fusing NS3 from HCV (Strain J4; Genotype 1b) to the MHC class II chaperone protein invariant chain (Ii). We found that, after a single vaccination of C57BL/6 or BALB/c mice with Ad-IiNS3, the HCV NS3-specific CD8(+) T cell responses were significantly enhanced, accelerated, and prolonged compared with the vaccine encoding NS3 alone. The AdIiNS3 vaccination induced polyfunctional CD8(+) T cells characterized by coproduction of IFN-gamma, TNF-alpha and IL-2, and this cell phenotype is associated with good viral control. The memory CD8(+) T cells also expressed high levels of CD27 and CD127, which are markers of long-term survival and maintenance of T cell memory. Functionally, the AdIiNS3-vaccinated mice had a significantly increased cytotoxic capacity compared with the AdNS3 group. The AdIiNS3-induced CD8(+) T cells protected mice from infection with recombinant vaccinia virus expressing HCV NS3 of heterologous 1b strains, and studies in knockout mice demonstrated that this protection was mediated primarily through IFN-gamma production. On the basis of these promising results, we suggest that this vaccination technology should be evaluated further in the chimpanzee HCV challenge model.
机译:针对丙型肝炎病毒(HCV)的非结构(NS)蛋白的强而广泛的细胞免疫应答与自发病毒清除相关。在这项研究中,我们通过将来自HCV的NS3(菌株J4;基因型1b)融合到II类MHC伴侣蛋白不变链(Ii)上,提高了基于腺病毒(Ad)的HCV疫苗的免疫原性。我们发现,在用Ad-IiNS3单次接种C57BL / 6或BALB / c小鼠后,与单独编码NS3的疫苗相比,HCV NS3特异性CD8(+)T细胞应答得到了显着增强,加速和延长。 AdIiNS3疫苗接种诱导的多功能CD8(+)T细胞,其特征为IFN-γ,TNF-α和IL-2的共同产生,并且该细胞表型与良好的病毒控制有关。记忆CD8(+)T细胞还表达高水平的CD27和CD127,这是T细胞记忆长期存活和维持的标志。在功能上,与AdNS3组相比,接种AdIiNS3的小鼠具有明显增加的细胞毒性能力。 AdIiNS3诱导的CD8(+)T细胞可保护小鼠免受表达异源1b株HCV NS3的重组牛痘病毒的感染,在剔除小鼠中的研究表明,这种保护作用主要是通过IFN-γ产生的。基于这些有希望的结果,我们建议应在黑猩猩HCV攻击模型中进一步评估这种疫苗接种技术。

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