ETEC EPIDEMIOLOGY AND VACCINE RESEARCH IN LOWER EGYPT

下埃及的 ETEC 流行病学和疫苗研究

• 批准号: 6108125
• 负责人: JOHN D CLEMENS
• 金额: --
• 依托单位: EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6108125
• 关键词: Egypt; Escherichia coli; age difference; antibody titering; bacterial antigens; bacterial vaccines; child (0-11); clinical research; diarrhea; disease /disorder proneness /risk; enterotoxins; epidemiology; human subject; immunization; infant human (0-1 year); interview; longitudinal human study; nonhuman therapy evaluation; phenotype; preschool child (1-5); vaccine development; virulence

Enterotoxigenic Escherichia coli (ETEC) diarrhea is hyperendemic among young Egyptian children, with a balanced distribution of toxin phenotypes from pathogenic isolates. These features make it logical to develop a field site for the evaluation of ETEC epidemiology and ETEC vaccines in Egypt. We are engaged in a collaborative program of research in lower Egypt designed to characterize ETEC diarrhea in a pediatric cohort and to test the safety and immunogenicity of a promising killed oral ETEC vaccine candidate in preparation for a field trial of vaccine efficacy. We have followed a cohort of children under 3 years with twice-weekly active surveillance in Abu Homos (Beheira governorate) to determine the age-specific incidence rate of ETEC diarrhea, by toxin and colonization factor (CFA) phenotypes. During 18 months of follow-up of 288 children in Abu Homos, ETEC was isoalted in 290 (24%) of the 1232 detected diarrheal episodes; the incidence rates of ETEC (episodes per child-year) were 1.5, 1.6, and 0.8 in the first, second, and third years of life. Concurrent with establishment of this surveillance, we conducted randomized, placebo-controlled Phase 2 studies of killed oral ETEC vaccine, administered as a two-dose regimen to 76 adults, 107 children aged 6-12 years, and and 106 children aged 2-5 years in Benha, near Cairo. Each of these studies demonstrated the vaccine to be well-tolerated and to induce significant musosal immune responses to vaccine antigens. A similarly designed trial of the vaccine, administered to infants will be launched during the coming months.

产肠毒素大肠杆菌（ETEC）腹泻在 年轻的埃及儿童，毒素表型分布均衡 从病原分离物中分离出来。 这些特征使得开发一个 评价ETEC流行病学和ETEC疫苗的现场 埃及 我们正在进行一项合作研究计划， 埃及旨在描述儿科队列中ETEC腹泻的特征， 检测有希望杀死的口服ETEC的安全性和免疫原性 候选疫苗，为疫苗效力的实地试验做准备。 我们跟踪了一组3岁以下的儿童，每周两次， 在Abu Homos（Beheira省）进行积极监测，以确定 按毒素和定植列出的ETEC腹泻的年龄特异性发病率 因子（CFA）表型。在18个月的随访期间， 在检测到的1232株大肠杆菌中，有290株（24%）分离出ETEC 事件; ETEC的发生率（每儿童年的事件）为1.5， 1.6，0.8在第一，第二，第三年的生活。并发 随着这项监测的建立，我们进行了随机， 口服ETEC灭活疫苗的安慰剂对照II期研究， 作为两剂方案给予76名成人，107名6-12岁的儿童 在开罗附近的Benha，有106名2至5岁的儿童。中的每 这些研究表明疫苗耐受性良好， 对疫苗抗原有显著的免疫应答。 类似 将启动针对婴儿的疫苗设计试验 在接下来的几个月里。