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识别可用于疫苗中的肠毒素大肠杆菌（ETEC）表面上的分子靶标。这些生物在全球范围内是严重腹泻病的最常见细菌原因，这是与旅行者中腹泻有关的最主要感染，也是美国腹泻病的新兴原因。尽管这些生物与全球人类健康有关，但目前尚无广泛的保护性ETEC疫苗。 这些研究将使用专门为此目的而设计的新最先进的技术平台。这些将包括DNA（基因）和蛋白质微阵列，由NIAID赞助的病原体功能基因组资源中心提供。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，使其非常有用的疫苗发现工具。该项目的目的是：目标1。缩进：（a）。从严重霍乱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。两组研究将使用PFGRC提供的ETEC特异性DNA微阵列。目标2。在小鼠或人类自然感染中通过抗体识别的凹痕蛋白。这些研究将使用PFGRC产生的质谱和蛋白质微阵列，包括质谱和蛋白质微阵列。目的3。最后，该项目将测试被确定为高度保守的蛋白质的保护性功效（AIM 1）并在最近发育的ETEC感染的成年小鼠模型中被识别（AIM 2）。纯化蛋白质后，将通过ETEC对小鼠进行免疫和挑战，以测试候选疫苗分子防止感染的能力。 公共卫生相关性：肠毒素大肠杆菌（ETEC）每年造成数百万人的感染和数十万人死亡。尽管这些感染在发展中国家占主导地位，并且在长期是旅行者腹泻的主要原因，但它们也负责美国最近发生的许多大规模爆发。这项研究的主要长期目标是通过开发ETEC疫苗来防止这些感染。