Novel Antigen Identification for an Enterotoxigenic E. coli Vaccine

产肠毒素大肠杆菌疫苗的新抗原鉴定

• 批准号: 8436769
• 负责人: James Michael Fleckenstein
• 金额: $ 25.96万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8436769
• 关键词: Novel; Antigen; Identification; Enterotoxigenic; E.

DESCRIPTION (provided by applicant): The long-term objective of this work is to identify molecular targets on the surface of enterotoxigenic E. coli (ETEC) that could be used in a vaccine. These organisms are globally the most common bacterial cause of serious diarrheal illness, perennially the most main infection associated with diarrhea in travelers, and an emerging cause of diarrheal illness in the US. Despite the relevance of these organisms to global human health, there is presently no broadly protective ETEC vaccine available. These studies will use newly available state-of the-art technology platforms designed specifically for this purpose. These will include both DNA (gene) and protein microarrays made available by the NIAID-sponsored Pathogen Functional Genomic Resource Center. Both the gene and protein microarrays encompass known or potential virulence factors from multiple ETEC strains making them extraordinarily useful tools for vaccine discovery. The aims of this project are: Aim 1. Indentify: (a). genes conserved among ETEC strains isolated from cases of severe cholera-like diarrheal illness, (b). virulence factors that are altered in response to infection. Both of sets of studies will use ETEC-specific DNA microarrays made available by the PFGRC. Aim 2. Indentify proteins that are recognized by antibodies following experimental infections in mice or natural infections in humans. These studies will use immuno-proteomic techniques including mass spectrometry and protein microarrays produced by the PFGRC. Aim 3. Finally, this project will test the protective efficacy of proteins identified as being both highly conserved (aim 1) and recognized during infection (aim 2) in a recently developed adult mouse model of ETEC infection. Following purification of the proteins, mice will be immunized and challenged with ETEC to test the ability of the candidate vaccine molecules to prevent infection. PUBLIC HEALTH RELEVANCE: Enterotoxigenic Escherichia coli (ETEC) are responsible for millions of infections and hundreds of thousands of deaths due to diarrhea annually. While these infections predominate in developing countries, and are perennially the major cause of traveler's diarrhea, they are also responsible for numerous recent large-scale outbreaks in the United States. The major long-term goal of this research is to prevent these infections by development of an ETEC vaccine.

描述（由申请人提供）：这项工作的长期目标是确定可用于疫苗的产肠毒素大肠杆菌（ETEC）表面的分子靶标。这些微生物是全球范围内严重腹泻疾病最常见的细菌原因，一直是与旅行者腹泻相关的最主要感染，也是美国腹泻疾病的新原因。尽管这些生物体与全球人类健康息息相关，但目前尚无具有广泛保护性的 ETEC 疫苗。 这些研究将使用专为此目的而设计的最新最先进的技术平台。这些将包括由 NIAID 赞助的病原体功能基因组资源中心提供的 DNA（基因）和蛋白质微阵列。基因和蛋白质微阵列都包含来自多种 ETEC 菌株的已知或潜在毒力因子，这使得它们成为疫苗发现的非常有用的工具。该项目的目标是： 目标 1. 确定：(a)。从严重霍乱样腹泻病例中分离出的 ETEC 菌株中保守的基因，(b)。因感染而改变的毒力因子。两组研究都将使用 PFGRC 提供的 ETEC 特异性 DNA 微阵列。目标 2. 鉴定小鼠实验感染或人类自然感染后抗体识别的蛋白质。这些研究将使用免疫蛋白质组学技术，包括 PFGRC 生产的质谱和蛋白质微阵列。目标 3。最后，该项目将在最近开发的 ETEC 感染成年小鼠模型中测试高度保守（目标 1）和感染期间识别（目标 2）的蛋白质的保护功效。纯化蛋白质后，将对小鼠进行免疫并用 ETEC 进行攻击，以测试候选疫苗分子预防感染的能力。 公共卫生相关性：产肠毒素大肠杆菌 (ETEC) 每年导致数百万例感染和数十万人因腹泻死亡。虽然这些感染在发展中国家占主导地位，并且一直是旅行者腹泻的主要原因，但它们也是美国最近多次大规模爆发的原因。这项研究的主要长期目标是通过开发 ETEC 疫苗来预防这些感染。