HCV多表位基因重组BCG活疫苗的构建及在小鼠体内诱导特异性免疫应答的研究

发布时间：2018-01-04 13:22

本文关键词：HCV多表位基因重组BCG活疫苗的构建及在小鼠体内诱导特异性免疫应答的研究　出处：《第四军医大学》2006年博士论文　论文类型：学位论文

【摘要】：丙型肝炎病毒(hepatitis C virus，HCV)是慢性肝炎、肝硬化等慢性肝病的主要致病因子之一，HCV急性感染后55～85％以上发展为慢性肝炎，其中约20％最终结局为肝硬化、肝细胞肿瘤或肝功能衰竭。世界范围内大约有1.7亿患者，我国感染人数大约为5000万，并有上升的趋势。目前对HCV感染的治疗除了重组α干扰素(INF-α)有一定疗效外，，仍无切实有效的抗病毒治疗方法，亟需发展有效的预防性和治疗性疫苗以防止其传播。目前HCV疫苗的研究主要集中在核酸疫苗、亚单位疫苗和病毒载体疫苗等方面，其共同不足是不能刺激理想的细胞免疫应答。而由于HCV包膜糖蛋白E2的中和性抗原位点存在高变区(hypervariable region，HVR)，使体液免疫为主的HCV预防性疫苗研究长期以来进展缓慢。因此，人们逐渐把目光转向以细胞免疫为主的预防和治疗性疫苗方面。本研究利用基因重组技术，把含HCV截短C基因、E2区模拟表位和非结构区的多个Th与CTL(主要为A2限制性)表位基因串联，多表位基因构建入大肠杆菌和分枝杆菌穿梭质粒，筛选分泌表达HCV多表位抗原的重组BCG(recombinant BCG，rBCG)，然后免疫BALB／c小鼠及
[Abstract]:Hepatitis C virus (HCV) is one of the main pathogenic factors of chronic hepatitis, cirrhosis and other chronic liver diseases. More than 55% of patients with HCV develop chronic hepatitis after acute infection. About 20% of them end up with cirrhosis, hepatocellular tumor or liver failure. There are about 170 million patients worldwide. The number of infected people in China is about 50 million, and there is a rising trend. At present, the treatment of HCV infection in addition to recombinant interferon 伪 INF- 伪) has a certain curative effect. There is still no effective antiviral treatment, and it is urgent to develop effective preventive and therapeutic vaccines to prevent their transmission. At present, the research of HCV vaccine is mainly focused on nucleic acid vaccine. Subunit vaccine and viral vector vaccine. The common deficiency is that it can not stimulate the ideal cellular immune response, but because of the existence of hypervariable region in the neutralizing antigen site of HCV envelope glycoprotein E2. Because of the slow progress in the study of humoral immune HCV prophylactic vaccines, people have gradually turned their attention to the preventive and therapeutic vaccines based on cellular immunity. In this study, a number of Th containing HCV truncated C gene E _ 2 region and non-structural region were connected with CTL (mainly A2 restricted) epitope gene by gene recombination technique. The polyepitope gene was constructed into Escherichia coli and Mycobacterium shuttle plasmid to screen recombinant BCG(recombinant BCGrBCGG secreting and expressing HCV polyepitope antigen. Then immunize BALB/c mice and
【学位授予单位】：第四军医大学
【学位级别】：博士
【学位授予年份】：2006
【分类号】：R392

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