HCV多表位基因重組BCG活疫苗的構(gòu)建及在小鼠體內(nèi)誘導(dǎo)特異性免疫應(yīng)答的研究
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本文關(guān)鍵詞:HCV多表位基因重組BCG活疫苗的構(gòu)建及在小鼠體內(nèi)誘導(dǎo)特異性免疫應(yīng)答的研究 出處:《第四軍醫(yī)大學(xué)》2006年博士論文 論文類(lèi)型:學(xué)位論文
更多相關(guān)文章: 丙型肝炎病毒(HCV) 表位 基因免疫 重組BCG 疫苗 免疫應(yīng)答
【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%以上發(fā)展為慢性肝炎,其中約20%最終結(jié)局為肝硬化、肝細(xì)胞腫瘤或肝功能衰竭。世界范圍內(nèi)大約有1.7億患者,我國(guó)感染人數(shù)大約為5000萬(wàn),并有上升的趨勢(shì)。目前對(duì)HCV感染的治療除了重組α干擾素(INF-α)有一定療效外,,仍無(wú)切實(shí)有效的抗病毒治療方法,亟需發(fā)展有效的預(yù)防性和治療性疫苗以防止其傳播。目前HCV疫苗的研究主要集中在核酸疫苗、亞單位疫苗和病毒載體疫苗等方面,其共同不足是不能刺激理想的細(xì)胞免疫應(yīng)答。而由于HCV包膜糖蛋白E2的中和性抗原位點(diǎn)存在高變區(qū)(hypervariable region,HVR),使體液免疫為主的HCV預(yù)防性疫苗研究長(zhǎng)期以來(lái)進(jìn)展緩慢。因此,人們逐漸把目光轉(zhuǎn)向以細(xì)胞免疫為主的預(yù)防和治療性疫苗方面。 本研究利用基因重組技術(shù),把含HCV截短C基因、E2區(qū)模擬表位和非結(jié)構(gòu)區(qū)的多個(gè)Th與CTL(主要為A2限制性)表位基因串聯(lián),多表位基因構(gòu)建入大腸桿菌和分枝桿菌穿梭質(zhì)粒,篩選分泌表達(dá)HCV多表位抗原的重組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 偽 INF- 偽) 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
【學(xué)位授予單位】:第四軍醫(yī)大學(xué)
【學(xué)位級(jí)別】:博士
【學(xué)位授予年份】:2006
【分類(lèi)號(hào)】:R392
【引證文獻(xiàn)】
相關(guān)碩士學(xué)位論文 前1條
1 張寧;以改造隱性表位為基礎(chǔ)的HIV復(fù)合多表位疫苗的構(gòu)建及其免疫應(yīng)答分析[D];第四軍醫(yī)大學(xué);2010年
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