本文選題：戊型肝炎病毒　切入點：表位疫苗　出處：《廈門大學(xué)》2009年碩士論文　論文類型：學(xué)位論文

【摘要】： 戊型肝炎是由戊型肝炎病毒引起的、經(jīng)消化道傳播的急性肝炎,在發(fā)展中國家及發(fā)達國家均有流行。越來越多的研究證據(jù)表明戊型肝炎為人獸共患病,其病毒潛在由動物到人的交叉感染而導(dǎo)致傳播的危險,這使得戊型肝炎逐漸成為嚴重威脅人類健康的疾病。由于至今尚未建立有效的病毒分離方法和細胞培養(yǎng)模型,也缺乏便捷實用的動物模型,國內(nèi)外學(xué)者對戊型肝炎病毒的研究還不夠充分。為提供更有效的疾病防治方案,人們迫切需要研究清楚戊型肝炎病毒的抗原表位結(jié)構(gòu)和免疫應(yīng)答機制。 本研究首先利用針對戊型肝炎病毒的抗體庫,采用基于改造蛋白和重疊肽庫的表位鑒定技術(shù)、抗體競爭抑制性分析、抗體免疫捕獲病毒分析、基于重組衣殼蛋白吸附細胞模型或病毒結(jié)合細胞模型的抗體性質(zhì)分析等方法,較詳盡地考察抗體的各種性質(zhì)。其次,分析對比了代表性表位,進行了序列比對、表位突變分析,這對認識戊型肝炎病毒復(fù)雜的抗原表位和疫苗設(shè)計有著重要的意義。再次,利用顆粒性蛋白載體構(gòu)建表位融合蛋白從而充分地展示了表位,發(fā)現(xiàn)了其中12A10抗體對應(yīng)的非優(yōu)勢表位具有一定的中和性,可以作為表位疫苗設(shè)計的候選表位。 本論文嘗試在戊型肝炎病毒重組衣殼蛋白的基礎(chǔ)上闡釋了戊型肝炎病毒抗原表位,篩選出具有代表性的表位并進行深入的分析比較,嘗試在這些表位基礎(chǔ)上對其表位疫苗設(shè)計進行了初步的探索。這不僅為表位的深入研究提供了方法參考和研究思路,有助于對戊型肝炎病毒抗原全面深入的了解;還有利于其病理研究和疫苗研制,對戊型肝炎病毒表位疫苗設(shè)計具有很好的參考價值。
[Abstract]:Hepatitis E is caused by hepatitis E virus. Acute hepatitis transmitted through digestive tract is prevalent in both developing and developed countries. The potential risk of transmission of the virus from animal to human cross-infection has made hepatitis E a serious threat to human health, since effective virus isolation methods and cell culture models have not yet been established. There is also a lack of convenient and practical animal models. The research on hepatitis E virus by domestic and foreign scholars is not enough. In order to provide more effective disease prevention and treatment programs, It is urgent to study the epitope structure and immune response mechanism of hepatitis E virus. In this study, the antibody library against hepatitis E virus, epitope identification based on modified protein and overlapping peptide library, antibody competitive inhibition analysis and antibody capture virus analysis were used. Based on the analysis of antibody properties of recombinant capsid protein adsorption cell model or virus binding cell model, the various properties of antibody were investigated in detail. Secondly, the representative epitopes were analyzed and compared, sequence alignment and epitope mutation analysis were carried out. This is of great significance in understanding the complex antigen epitopes of hepatitis E virus and vaccine design. Thirdly, epitope fusion proteins are constructed using granular protein vectors to fully display epitopes. It was found that the non-dominant epitopes corresponding to 12A10 antibody were neutralized and could be used as candidate epitopes for epitope vaccine design. Based on the recombinant capsid protein of hepatitis E virus, the epitopes of hepatitis E virus were elucidated, and the representative epitopes were screened and compared. On the basis of these epitopes, this paper attempts to explore the design of the epitope vaccine, which not only provides a method reference for the further study of the epitopes, but also contributes to the thorough understanding of hepatitis E virus antigen. It is also beneficial to the pathological research and vaccine development, and has a good reference value for the design of hepatitis E virus epitope vaccine.
【學(xué)位授予單位】：廈門大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2009
【分類號】：R392

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