嗜肺军团菌DNA疫苗的初步研究

发布时间：2018-03-10 04:22

本文选题：嗜肺军团菌　切入点：DNA疫苗　出处：《四川大学》2006年博士论文　论文类型：学位论文

【摘要】：军团病(Legionnaire's disease)是由于吸入含有致病性军团菌感染所致的一种以非典型肺炎或Pantiac热为主要表现常伴多系统损害的急性细菌性传染病，病程进展快，免疫功能低下者易感，由于其症状不典型，常被误诊误治，病死率高，易暴发流行。军团菌广泛存在于土壤、江河湖等天然水、井水和自来水生活用水、现代城市广泛使用的空调的冷却塔水、加湿器内水及其它人工水环境在内各种水体环境中，是一种革兰氏阴性兼性菌，可寄生于原虫中，作为一种病原体，它可侵入哺乳动物巨噬细胞，逃避吞噬体和溶酶体的杀伤作用，并在其中生长繁殖。军团菌目前已发现有48种70个血清型，致病性军团菌主要包括嗜肺军团菌(Legionella pneumophila)血清1～15型、L．micdadei、L．gormanii、L．bozemanii等，其中嗜肺军团菌占96.4％；在美国，90％的军团病由嗜肺军团菌引起，而其中79％为血清1型(LP1)。我国及其它许多国家已将军团病列为需要重点防治的一种新发传染病，但目前尚无理想的防治措施，因此，研制出安全有效的疫苗对军团病防治具有重要的现实意义。本研究在查阅分析国内外相关文献及结合本室研究进展的基础上，选定嗜肺军团菌DNA疫苗作为研究方向，具体选择了lvgA基因、htpA和Hsp60基因为疫苗候选基因，并将免疫刺激序列CpG基序构建于lvgA基因侧翼，以及采用重组PCR法实现了嗜肺军团菌lvgA及Hsp60基因融合，构建了lvgA基因、引入CpG基序的lvgA基因及lvgA／Hsp60融合基因的重组真核表达载体等疫苗，并检测其免疫原性和免疫保护性指标，，为最终研制出新一代安全、高效嗜肺军团菌DNA疫苗提供了一定的实验依据。
[Abstract]:Legionnaive disease is an acute bacterial infectious disease caused by inhalation of Legionnaire's disease, which is characterized by atypical pneumonia or Pantiac fever. Legionella is widely found in soil, rivers and lakes, natural water, well water and tap water, cooling tower water of air conditioning, which is widely used in modern cities. Water and other artificial water environments in humidifiers are gram-negative facultative bacteria that parasitize protozoa and, as a pathogen, invade mammalian macrophages. There are 48 kinds of 70 serotypes found in Legionella pneumophilia serotypes. The pathogenic Legionella pneumophila serotype 115 type L.micdadei L.gormaniiania L.bozemanii, and so on, have been found in Legionella pneumophila. In the United States, 90% of Legionnaires' disease is caused by Legionella pneumophila, and 79% of them are serotype 1 LP1.Legionnaires' disease has been listed as a new infectious disease in China and many other countries. However, there is no ideal prevention and cure measures at present. Therefore, it is of great practical significance to develop a safe and effective vaccine for the prevention and treatment of Legionnaires disease. The DNA vaccine of Legionella pneumophila was selected as the research direction. LvgA gene htpA and Hsp60 gene were selected as candidate genes, and the CpG motif of the immunostimulatory sequence was constructed on the flanking of lvgA gene. The fusion of lvgA and Hsp60 genes of Legionella pneumophila was achieved by recombinant PCR method, and the lvgA gene was constructed. The recombinant eukaryotic expression vector of CpG motif lvgA gene and lvgA/Hsp60 fusion gene were introduced, and the immunogenicity and immunological protective indexes were detected. It provides a certain experimental basis for the development of a new generation of safe and effective Legionella pneumophila DNA vaccine.
【学位授予单位】：四川大学
【学位级别】：博士
【学位授予年份】：2006
【分类号】：R392

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