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: 8487344
• 负责人: James Michael Fleckenstein
• 金额: $ 25.75万
• 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/8487344
• 关键词: Address; Adherence; Adult; Animal Experimentation; Antibodies; Antigens; Bangladesh; Categories; Cessation of life; Child; Cholera; Collection; Complement; Complex; DNA; DNA Microarray Chip; Data; Developing Countries; Development; Diarrhea; Disease; Disease Association; Disease Outbreaks; Escherichia coli; Escherichia coli Infections; Escherichia coli Proteins; Escherichia coli Vaccines; Expression Library; Gene Proteins; Genes; Genome; Genomics; Goals; Health; Human; Immune response; In Vitro; Infection; Infection prevention; International; Intestines; Laboratories; Mass Spectrum Analysis; Modeling; Molecular; Molecular Target; Mouse Protein; Mus; National Institute of Allergy and Infectious Disease; Organism; Pathogenesis; Patients; Plasmids; Production; Protein Microchips; Proteins; Proteome; Proteomics; Recombinants; Research; Research Personnel; Resources; Serum; Solid; Surface; Surface Antigens; Techniques; Technology; Testing; Traveler' s diarrhea; United States; Vaccines; Validation; Virulence; Virulence Factors; Work; base; comparative; comparative genomic hybridization; design; enterotoxigenic Escherichia coli; functional genomics; immunogenic; immunogenicity; indexing; mouse model; novel; novel vaccines; pathogen; protective efficacy; protein purification; public health relevance; response; tool; vaccine candidate; vaccine development

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.

描述(申请人提供)：这项工作的长期目标是确定产肠毒素大肠杆菌(ETEC)表面可用于疫苗的分子靶点。这些细菌是全球最常见的严重腹泻疾病的细菌病因，是与旅行者腹泻有关的最主要感染，也是美国腹泻疾病的新病因。尽管这些生物与全球人类健康相关，但目前还没有广泛保护性的ETEC疫苗可用。这些研究将使用专门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个ETEC菌株的已知或潜在的毒力因子，使它们成为疫苗发现的非常有用的工具。本项目的目标是：目标1.确定：(A)从严重霍乱样腹泻疾病病例中分离的ETEC菌株之间的保守基因，(B)。毒力因子因感染而改变的毒力因子。这两组研究都将使用PFGRC提供的ETEC特异性DNA微阵列。目的2.鉴定小鼠实验感染或人类自然感染后被抗体识别的蛋白质。这些研究将使用免疫蛋白质组学技术，包括由PFGRC生产的质谱学和蛋白质微阵列。目的3.最后，本项目将在最近发展的ETEC感染成年小鼠模型中测试被鉴定为高度保守(目标1)和感染期间识别(目标2)的蛋白质的保护效果。纯化蛋白质后，将对小鼠进行免疫，并用ETEC挑战，以测试候选疫苗分子预防感染的能力。