乳酸杆菌膜表达幽门螺杆菌黏附素HpaA的活菌载体疫苗株的构建及保护效果研究

发布时间：2018-01-08 21:10

本文关键词：乳酸杆菌膜表达幽门螺杆菌黏附素HpaA的活菌载体疫苗株的构建及保护效果研究　出处：《四川大学》2006年博士论文　论文类型：学位论文

【摘要】：背景及目的：幽门螺杆菌(Helicobacter pylori，Hp)是慢性胃炎、消化性溃疡的主要致病因素，也是胃癌和胃黏膜相关淋巴组织淋巴瘤的主要诱发因子，世界卫生组织已将其列为Ⅰ类致癌物质。据调查，全球约有一半人存在着Hp感染，是迄今所知人类感染率最高的慢性感染性细菌。以抗生素为主的三联疗法具有费用高、患者依从性差、耐药菌增加及肠道菌群失调等缺点，难以应用于全球范围内的Hp控制。特别是对于占绝大多数的无症状感染者和儿童感染者是否需要应用抗生素治疗仍存在很大争议。疫苗将成为控制Hp感染最经济有效的手段。迄今为止，，包括超声粉碎菌体及重组亚单位蛋白等多种Hp抗原已经有了广泛研究甚至进入临床试验，并已采取了多种免疫方案。结果表明，绝大多数疫苗由于免疫原性有限，需要同时应用CT和LT之类的强效佐剂方能引起有效的保护性免疫，而这些佐剂具有一定的毒性限制了其人体应用。以减毒沙门菌作为载体所构建的活菌疫苗能够部分保护机体抵抗Hp感染，但同样具有潜在毒性难以在人群中广泛应用，特别是对婴儿和老人等免疫力较低的人群。乳酸杆菌是人体正常菌群，以其作为疫苗传递载体具有很多优点。作为食品生产和保存添加剂，乳酸杆菌在世界范围内已经有几百年的应用历史，具有公认的安全性。
[Abstract]:Background and objective: Helicobacter pylori (Helicobacter pylori Hp) is a chronic gastritis, the main pathogenic factor for peptic ulcer, and gastric cancer and gastric mucosa associated lymphoid tissue lymphoma of the main inducing factor, the WHO has been classified as a class I carcinogen. According to the survey, about half of the world the existence of Hp infection. Is known to the human infection rate of chronic bacterial infection. The highest triple therapy by antibiotics with high cost, poor patient compliance, drug resistant strains and disorder of intestinal flora and other shortcomings, Hp control is difficult to be applied in the global scope. Especially the need for antibiotic treatment for asymptomatic infection and children the majority of infected persons still controversial. Vaccine control Hp infection will become the most economical and effective means. So far, including a variety of ultrasonic crushing bacteria and the recombinant subunit protein. Hp antigen has been widely research even in clinical trials, and has taken a variety of immune scheme. The results show that the vast majority of vaccines due to limited immunogenicity, requires intensive adjuvant application of CT and LT at the same time, can induce protective immune adjuvant, which has certain toxicity limits its application in human body. Attenuated Salmonella as live vaccine vector constructed to protect against Hp infection, but also has potential toxicity can not be widely used in the crowd, especially for infants and the elderly people with low immunity.
Lactobacillus is a normal human flora. As a vaccine delivery carrier, lactobacilli has many advantages. As a food production and storage additive, lactobacillus has been applied in the world for hundreds of years, and it has generally recognized safety.

【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】：R392.1

【引证文献】