Novel Antigen Identification for an Enterotoxigenic E. coli Vaccine

 描述(申请人提供)：这项工作的重点是产肠毒素大肠杆菌(ETEC)，这是全球最常见的严重腹泻疾病的细菌原因。这些疾病威胁着世界贫困地区许多儿童的生命，那里的卫生设施和清洁水十分有限。虽然人们很早就知道，以前感染这些微生物可以提供保护，防止以后感染，但这种保护的性质尚不清楚。这些研究的长期目标是解决ETEC调查人员试图为这些生物体开发疫苗时未能解决的非常基本的问题：1.感染后感染的人对哪些蛋白质产生抗体反应？“这些反应中，哪些似乎与对ETEC的保护有关？”“我们能证明这些蛋白质在疫苗中触发保护性免疫反应吗？”迄今为止的研究表明，ETEC感染后的免疫反应实际上是相当复杂的，需要识别许多蛋白质。可以添加一些不属于目前正在测试的疫苗的新蛋白质，以提高这些疫苗的覆盖率和功能。这项提议的基本目标是加速发现新的保护性蛋白，并将其用途转化为有效的ETEC疫苗成分。解决这些根本问题将填补我们对ETEC感染后产生的保护性免疫反应理解的重要空白，并允许采取更合理的方法来开发针对这些具有全球重要性的病原体的广泛保护性疫苗。

 DESCRIPTION (provided by applicant): This work focuses on enterotoxigenic Escherichia coli (ETEC), globally the most common bacterial cause of serious diarrheal illness. These illnesses threaten the lives of many children in poor regions of the world where sanitation and clean water are limited. While it has long been known that prior infections with these organisms offer protection against later infection, the nature of the protection is not known. The long-term goal o these studies is to address very basic questions that have eluded ETEC investigators trying to develop vaccines for these organisms: 1."To what proteins do infected people mount antibody responses after infection?" 2. "Which of these responses appear to be associated with protection against ETEC?" 3. "Can we show that these proteins trigger protective immune responses in a vaccine?" Studies to date have shown us that the immune response following ETEC infection is actually quite complicated, with recognition of many proteins. Some novel proteins that are not part of vaccines currently being tested could be added to improve the coverage and function of these vaccines. The basic goals of this proposal are to accelerate the discovery of novel protective proteins and to translate their use into effective ETEC vaccine components. Addressing these fundamental questions will fill important gaps in our understanding of protective immune responses that develop following ETEC infections, and permit a more rational approach to development of a broadly protective vaccine for these pathogens of global importance.