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Immunogenicity of an influenza virus-vectored vaccine carrying the hepatitis C virus protein epitopes in mice
Antiviral Research ( IF 7.6 ) Pub Date : 2017-08-01 , DOI: 10.1016/j.antiviral.2017.07.015
Shaogeng Zhang , Fang Sun , Tianyu Ren , Yueqiang Duan , Hongjing Gu , Chengcai Lai , Zhaohai Wang , Peirui Zhang , Xiliang Wang , Penghui Yang

Hepatitis C virus (HCV) has a devastating impact on human health, and infections can progress into liver fibrosis, cirrhosis, and hepatocellular carcinoma. There is no effective HCV vaccine. In this study, we rescued a recombinant PR8 influenza viral vector, called rgFLU-HCVCE1E2, carrying the core and envelope glycoprotein (C/E1/E2) epitopes of HCV inserted into the influenza nonstructural protein 1 gene. The morphological characteristics of rgFLU-HCVCE1E2 and the expression of the C/E1/E2 epitopes of HCV were examined. rgFLU-HCVCE1E2 replicated in various cell lines, including MDCK, A549, and Huh7.5 cells. More importantly, in BALB/c mice immunized intranasally twice at a 21-day interval with 104, 105, or 106 TCID50 rgFLU-HCVCE1E2, the viral vector induced a robust antibody response to influenza and HCV and potent IFN-γ and IL-4 secretion in response to HCV antigens in a dose-dependent manner. The rgFLU-HCVCE1E2 virus also stimulated IFN-γ production by virus-specific peripheral blood mononuclear cells in patients with chronic HCV infection. The study demonstrated that rgFLU-HCVCE1E2 carrying HCV antigens is immunogenic in vivo and has potential for the development of a HCV vaccine.



中文翻译:

带有丙型肝炎病毒蛋白抗原决定簇的流感病毒载体疫苗在小鼠中的免疫原性

丙型肝炎病毒(HCV)对人类健康具有毁灭性影响,感染可能会发展为肝纤维化,肝硬化和肝细胞癌。没有有效的HCV疫苗。在这项研究中,我们拯救了重组PR8流感病毒载体,称为rgFLU-HCV CE1E2,携带携带插入流感非结构蛋白1基因的HCV核心和包膜糖蛋白(C / E1 / E2)表位。检查rgFLU-HCV CE1E2的形态特征和HCV C / E1 / E2表位的表达。rgFLU-HCV CE1E2在各种细胞系中复制,包括MDCK,A549和Huh7.5细胞。更重要的是,在BALB / c小鼠鼻内免疫两次在21天的间隔用10 4,10 5,或10 6 TCID 50 rgFLU-HCV CE1E2,病毒载体以剂量依赖的方式诱导了对流感和HCV的强烈抗体反应以及对HCV抗原的有效IFN-γ和IL-4分泌。rgFLU-HCV CE1E2病毒还刺激了慢性HCV感染患者的病毒特异性外周血单核细胞产生的IFN-γ产生。该研究表明,携带HCV抗原的rgFLU-HCV CE1E2具有体内免疫原性并具有开发HCV疫苗的潜力。

更新日期:2017-08-01
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