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

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 产肠毒素大肠大肠杆菌（ETEC）是发展中国家儿童中常见的导致严重腹泻的细菌。 ETEC也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，开发一种可以预防ETEC的抗体制剂。 该制剂来源于接种ETEC表面蛋白的奶牛的乳汁。 为了测试奶牛的牛奶制备，志愿者将进入研究机构，每天三次在餐后饮用抗体制备物或安慰剂，持续7天。 在第三天，他们将摄入足以在至少60%的未受保护受试者中引起腹泻的ETEC剂量。 如果抗体制剂能保护ETEC攻击，则服用抗体制剂的受试者患病人数少于服用安慰剂的受试者。 在进行攻毒研究之前，进行了一项小型试验，以检测将用于攻毒的ETEC菌株。 5名年龄为18至45岁的健康受试者入住GCRC。 第二天，他们吃了清淡的早餐，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。 在这次挑战后，他们被密切监测，所有的粪便被收集，分级，并称重，以确定有多少受试者 在第5天，或更早（如有指征），他们开始使用抗生素根除攻毒株。 他们在第7天出院。 如上所述，该攻毒模型将用于检测牛抗体制剂。 此外，将使用相同的攻毒株评价潜在的ETEC疫苗株。

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.