戊型肝炎病毒衣壳蛋白的线性中和性表位的研究及其一种表位疫苗的设计与构建

发布时间：2018-03-07 13:11

本文选题：戊型肝炎病毒　切入点：表位疫苗　出处：《厦门大学》2009年硕士论文　论文类型：学位论文

【摘要】： 戊型肝炎是由戊型肝炎病毒引起的、经消化道传播的急性肝炎,在发展中国家及发达国家均有流行。越来越多的研究证据表明戊型肝炎为人兽共患病,其病毒潜在由动物到人的交叉感染而导致传播的危险,这使得戊型肝炎逐渐成为严重威胁人类健康的疾病。由于至今尚未建立有效的病毒分离方法和细胞培养模型,也缺乏便捷实用的动物模型,国内外学者对戊型肝炎病毒的研究还不够充分。为提供更有效的疾病防治方案,人们迫切需要研究清楚戊型肝炎病毒的抗原表位结构和免疫应答机制。本研究首先利用针对戊型肝炎病毒的抗体库,采用基于改造蛋白和重叠肽库的表位鉴定技术、抗体竞争抑制性分析、抗体免疫捕获病毒分析、基于重组衣壳蛋白吸附细胞模型或病毒结合细胞模型的抗体性质分析等方法,较详尽地考察抗体的各种性质。其次,分析对比了代表性表位,进行了序列比对、表位突变分析,这对认识戊型肝炎病毒复杂的抗原表位和疫苗设计有着重要的意义。再次,利用颗粒性蛋白载体构建表位融合蛋白从而充分地展示了表位,发现了其中12A10抗体对应的非优势表位具有一定的中和性,可以作为表位疫苗设计的候选表位。本论文尝试在戊型肝炎病毒重组衣壳蛋白的基础上阐释了戊型肝炎病毒抗原表位,筛选出具有代表性的表位并进行深入的分析比较,尝试在这些表位基础上对其表位疫苗设计进行了初步的探索。这不仅为表位的深入研究提供了方法参考和研究思路,有助于对戊型肝炎病毒抗原全面深入的了解;还有利于其病理研究和疫苗研制,对戊型肝炎病毒表位疫苗设计具有很好的参考价值。
[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.
【学位授予单位】：厦门大学
【学位级别】：硕士
【学位授予年份】：2009
【分类号】：R392

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