VALIDATION STUDY OF H10407 ENTEROTOXIGENIC E COLI (ETEC) CHALLENGE STRAIN

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。产肠毒素大肠杆菌(ETEC)是发展中国家儿童严重腹泻的常见致病菌。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的研究人员合作，开发一种可能预防ETEC的抗体制剂。该制剂是从接种ETEC表面蛋白的奶牛的牛奶中提取的。为了测试奶牛的牛奶制剂，志愿者将被允许进入研究机构，每天三次，饭后饮用抗体制剂或安慰剂，为期7天。第三天，他们将摄入足以导致至少60%无保护措施受试者腹泻的ETEC剂量。如果抗体制剂可以抵御ETEC的挑战，服用抗体制剂的受试者比服用安慰剂的受试者患病的人数更少。在进行挑战研究之前，进行了一项小规模试验，以测试将用于挑战的ETEC菌株。五名年龄介乎18至45岁的健康人士入院接受治疗。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，他们被密切监测，所有的粪便都被收集、分级和称重，以确定有多少受试者在第5天或更早(如果有指示)开始使用抗生素来根除挑战菌株。他们在第7天出院。如上所述，这个挑战模型将用于测试牛抗体制剂。此外，同一挑战毒株将用于评估潜在的ETEC疫苗毒株。

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.