E. coli O157: H7 Vaccine Development

大肠杆菌 O157：H7 疫苗开发

基本信息

批准号：
8339440
负责人：
Alfredo G Torres
金额：
$ 19.13万
依托单位：
UNIVERSITY OF TEXAS MED BR GALVESTON
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-09-27 至 2014-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8339440
关键词：
Acute Renal Failure with Renal Papillary Necrosis Affect Agriculture Antigens Ballistics Bioinformatics Bioterrorism Categories Centers for Disease Control and Prevention (U.S.)Child Childhood Injury Code DNA Development Diarrhea Disease Dose Elderly Escherichia coli Escherichia coli EHEC Escherichia coli Infections Escherichia coli O157 Expression Library Food Genes Genome Goals Gram-Negative Bacteria Hemolytic-Uremic Syndrome Human Immune response Immunity Immunization Infection Infection prevention Investigation Knowledge Membrane Modeling Morbidity - disease rate Mus Pathogenesis Prevention Proteins Route Serotyping Subunit Vaccines Surface Testing Vaccinated Vaccines Virulence Virulence Factors Work biothreat extracellular mortality novel older patient pathogen pathogenic Escherichia coli prevent trait vaccine candidate vaccine development vaccine evaluation

项目摘要

DESCRIPTION (provided by applicant): Our long-term goal is to develop human vaccines for the prevention of diarrhea and/or HUS caused by E. coli O157:H7 and diarrhea by other pathogenic E. coli. In the currently proposed studies, we will screen the genome of E. coli O157:H7 to identify protective antigens that would become components of a human vaccine, and such approach can be used to protect against pathogenic E. coli infections without affecting commensal flora. The central hypothesis is that identification of protective antigens unique to O157:H7 is a viable approach for development of a vaccine for prevention of diarrhea and Hemolytic Uremic Syndrome episodes. Progress in recent years identifying E. coli O157:H7 novel virulence factors suggest that they can become useful components of a vaccine candidate. Of particular note are those proteins expressed on the bacterial membranes or secreted to the extracellular milieu, which have been previously associated with virulence traits. Therefore, it is plausible to propose that E. coli O157:H7-specific genes can become excellent candidates as components of vaccines. Our proposed experimental approach will focus on two specific aims: Identify the O157-specific gene sequences of E. coli O157:H7 and use them to generate a library of expression constructs optimized for vaccine screening; and determine the protective capacity of O157-specific gene sequence using a murine model of E. coli O157:H7 infection, to identify a subset of subunit vaccine candidates. Our proposal is significant because it is expected to provide the basic knowledge needed to develop an optimal vaccine that will be used to prevent infections caused by E. coli O157:H7, a category B pathogen for its potential use as biothreat agents in food and agriculture, and eventually to treat infections caused by other related pathogenic E. coli strains.

描述（由申请人提供）：我们的长期目标是开发人类疫苗，用于预防大肠杆菌 O157:H7 引起的腹泻和/或 HUS 以及其他致病性大肠杆菌引起的腹泻。在目前提出的研究中，我们将筛选大肠杆菌 O157:H7 的基因组，以鉴定将成为人类疫苗成分的保护性抗原，这种方法可用于防止致病性大肠杆菌感染，而不影响共生菌群。核心假设是，鉴定 O157:H7 特有的保护性抗原是开发预防腹泻和溶血性尿毒症综合征发作的疫苗的可行方法。近年来鉴定大肠杆菌 O157:H7 新型毒力因子的进展表明它们可以成为候选疫苗的有用成分。特别值得注意的是那些在细菌膜上表达或分泌到细胞外环境的蛋白质，这些蛋白质先前已被认为与毒力特征相关。因此，有理由认为大肠杆菌 O157:H7 特异性基因可以成为疫苗成分的优秀候选基因。我们提出的实验方法将侧重于两个具体目标：识别大肠杆菌 O157:H7 的 O157 特异性基因序列，并使用它们生成针对疫苗筛选优化的表达构建体文库；并使用大肠杆菌 O157:H7 感染的鼠模型确定 O157 特异性基因序列的保护能力，以确定候选亚单位疫苗的子集。我们的提案意义重大，因为它有望提供开发最佳疫苗所需的基础知识，该疫苗将用于预防大肠杆菌 O157:H7 引起的感染，大肠杆菌 O157:H7 是一种 B 类病原体，有可能用作食品和农业中的生物威胁剂，并最终治疗由其他相关致病性大肠杆菌菌株引起的感染。