DOSE-FINDING STUDY OF ENTEROTOXIGENIC E COLI (ETEC) CHALLENGE STRAIN

肠毒性大肠杆菌 (ETEC) 挑战菌株的剂量探索研究

• 批准号: 7604666
• 负责人: ROBIN MCKENZIE
• 金额: $ 0.95万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-12-01 至 2007-09-16
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7604666
• 关键词: Antibiotics; Antibodies; Bacteria; Bos taurus; Cattle; Child; Computer Retrieval of Information on Scientific Projects Database; Developed Countries; Developing Countries; Diarrhea; Dose; Eating; Escherichia coli Vaccines; Fasting; Feces; Funding; Grant; Immunization; Institution; Light; Membrane Proteins; Military Personnel; Milk; Modeling; Monitor; Placebos; Preparation; Research; Research Personnel; Resources; Source; Testing; Time; United States National Institutes of Health; Vaccinated; aged; day; drinking; enterotoxigenic Escherichia coli; research facility; volunteer

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Enterotoxigenic E. coli (ETEC) are bacteria that commonly cause severe diarrhea among children in developing countries. ETEC also cause diarrhea in travelers and military personnel in developing countries. Investigators in the Center for Immunization Research at Johns Hopkins are collaborating with investigators from the Navy to develop an antibody preparation that may protect against ETEC. The preparation is derived from the milk of cows vaccinated with proteins from the surface of ETEC. To test the cows' milk preparation, volunteers will be admitted to a research facility and drink an antibody preparation or a placebo three times per day, after meals, for 7 days. On the third day they will ingest a dose of ETEC that is sufficient to cause diarrhea in at least 60% of unprotected subjects. If the antibody preparation protects against the ETEC challenge, fewer subjects ingesting the antibody preparation will get sick than those ingesting placebo. Before carrying out the challenge study, a small trial was conducted to test the ETEC strain that will be used for the challenge. Five healthy subjects aged 18 to 45 were admitted to the GCRC. The next day they ate a light breakfast, fasted for 90 minutes, and ingested ETEC strain H10407 at a dose of 10(9) CFU, and then fasted for 90 more minutes. After this challenge they were monitored closely, and all stools were collected, graded, and weighed to determine how many subjects On Day 5, or sooner if indicated, they began antibiotics to eradicate the challenge strain. They were discharged by Day 7. As noted above, this challenge model will be used to test a bovine antibody preparation. In addition, the same challenge strain will be used to evaluate potential ETEC vaccine strains.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 产肠毒素大肠杆菌 (ETEC) 是一种通常导致发展中国家儿童严重腹泻的细菌。 ETEC 还会导致发展中国家的旅行者和军事人员腹泻。 约翰霍普金斯大学免疫研究中心的研究人员正在与海军研究人员合作开发一种可以预防 ETEC 的抗体制剂。 该制剂源自接种了 ETEC 表面蛋白质的牛乳。 为了测试牛奶制剂，志愿者将进入研究机构，每天饭后饮用抗体制剂或安慰剂 3 次，持续 7 天。 第三天，他们将摄入一定剂量的 ETEC，该剂量足以引起至少 60% 未受保护的受试者腹泻。 如果抗体制剂可以抵御 ETEC 攻击，那么摄入抗体制剂的受试者比摄入安慰剂的受试者会更少。 在进行挑战研究之前，进行了一项小型试验来测试将用于挑战的 ETEC 菌株。 GCRC 收治了 5 名年龄在 18 至 45 岁之间的健康受试者。 第二天，他们吃了一顿清淡的早餐，禁食 90 分钟，并以 10(9) CFU 的剂量摄入 ETEC 菌株 H10407，然后再禁食 90 分钟。 在这次挑战之后，他们受到密切监测，所有粪便都被收集、分级和称重，以确定有多少受试者在第 5 天或如果有指示的话更早开始使用抗生素来根除挑战菌株。 他们在第 7 天就出院了。 如上所述，该攻击模型将用于测试牛抗体制剂。 此外，相同的攻击株将用于评估潜在的 ETEC 疫苗株。