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Abstract：
The nucleoprotein (NP) is a vital target for the heterosubtypic immunity of CD8+ cytotoxic T lymphocytes (CTLs) due to its conservation among influenza virus subtypes. To further enhance the T cell immunity of NP, autophagy-inducing peptide C5 (AIP-C5) from the CFP10 protein of Mycobacterium tuberculosis was used. Mice were immunized intranasally (i.n.) with human adenoviral vectors, HAd-C5-NP(H7N9) or HAd-NP(H7N9), expressing NP of an H7N9 influenza virus with or without the AIP-C5, respectively. Both vaccines developed similar levels of NP-specific systemic and mucosal antibody titers; however, there was a significantly higher number of NP-specific CD8 T cells secreting interferon-gamma (IFN-γ) in the HAd-C5-NP(H7N9) group than in the HAd-NP(H7N9) group. The HAd-C5-NP(H7N9) vaccine provided better protection following the challenge with A/Puerto Rico/8/1934(H1N1), A/Hong Kong/1/68(H3N2), A/chukkar/MN/14951-7/1998(H5N2), A/goose/Nebraska/17097/2011(H7N9), or A/Hong Kong/1073/1999(H9N2) influenza viruses compared to the HAd-NP(H7N9) group. The autophagy transcriptomic gene analysis of the HAd-C5-NP(H7N9) group revealed the upregulation of some genes involved in the positive regulation of the autophagy process. The results support further exploring the use of NP and AIP-C5 for developing a universal influenza vaccine for pandemic preparedness.
摘要：
核蛋白（NP）由于其在流感病毒亚型中的保守性，因此是CD8细胞毒性T淋巴细胞（CTL）异亚型免疫的重要靶标。为了进一步增强NP的T细胞免疫，使用来自结核分枝杆菌CFP10蛋白的自噬诱导肽C5(AIP-C5)。用人腺病毒载体鼻内(i.n.)免疫小鼠,HAd-C5-NP(H7N9)或HAd-NP(H7N9),在分别具有或不具有AIP-C5的情况下表达H7N9流感病毒的NP。两种疫苗的NP特异性全身和粘膜抗体滴度水平相似；然而，HAd-C5-NP（H7N9）组分泌干扰素-γ（IFN-γ）的NP特异性CD8T细胞数量明显高于HAd-NP（H7N9）组。HAd-C5-NP（H7N9）疫苗在A/PuertoRico/8/1934（H1N1）攻击后提供了更好的保护，A/HongKong/1/68(H3N2),A/chukkar/MN/14951-7/1998(H5N2),A/鹅/内布拉斯加州/17097/2011（H7N9），或与HAd-NP（H7N9）组相比的A/HongKong/1073/1999（H9N2）流感病毒。HAd-C5-NP（H7N9）组的自噬转录组基因分析揭示了一些参与自噬过程正调控的基因的上调。结果支持进一步探索使用NP和AIP-C5开发用于大流行准备的通用流感疫苗。
