E. coli O157: H7 Vaccine Development

描述（由申请人提供）：我们的长期目标是开发用于预防由大肠杆菌引起的腹泻和/或HUS的人类疫苗。大肠杆菌O 157：H7引起的腹泻和其它致病性大肠杆菌引起的腹泻。杆菌在目前的研究中，我们将筛选E. coli O 157：H7中筛选出保护性抗原，并将其作为人源性疫苗的组成部分。大肠杆菌感染而不影响植物植物群。核心假设是，鉴定O 157：H7特有的保护性抗原是开发预防腹泻和溶血性尿毒综合征发作的疫苗的可行方法。近年来在鉴定E. coli O 157：H7新毒力因子的研究表明，它们可以成为候选疫苗的有用组分。特别值得注意的是在细菌膜上表达或分泌到细胞外环境的那些蛋白质，其先前已与毒力性状相关。因此，我们有理由认为E.大肠杆菌O 157：H7特异性基因可以成为疫苗组分的良好候选者。我们提出的实验方法将集中在两个具体的目标：确定O 157特异性基因序列的E。coliO 157：H7中表达，构建了一个优化的表达文库用于疫苗筛选，并利用小鼠大肠杆菌模型测定O 157特异性基因序列的保护能力。coli O 157：H7感染，以鉴定亚单位疫苗候选物的子集。我们的建议是重要的，因为它有望提供开发最佳疫苗所需的基本知识，该疫苗将用于预防由E.大肠杆菌O 157：H7，一种B类病原体，在食品和农业中具有潜在的生物威胁剂的用途，并最终用于治疗由其他相关致病性E.大肠杆菌菌株。 公共卫生相关性：我们的目标是筛选E。coli O 157：H7（B类病原体）中鉴定保护性抗原，所述保护性抗原将在开发人疫苗中成为疫苗候选物的组分。

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. PUBLIC HEALTH RELEVANCE: Our objective is to screen the genome of E. coli O157:H7 (category B pathogen) to identify protective antigens that would become components of vaccine candidates in developing a human vaccine.