CAMPYLOBACTER JEJUNI CHALLENGE: ASSESSMENT OF HOMOLOGOUS PROTECTION

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 这项研究的目标是继续发展一种感染空肠弯曲杆菌的模型，这是一种导致食物和水传播疾病(主要是腹泻)的细菌。其目的是1)确定健康受试者是否对空肠弯曲菌再次感染形成短期(不到6个月)的保护；以及2)表征对空肠弯曲菌感染的免疫反应。获得的信息将用于开发针对弯曲杆菌感染的疫苗。 志愿者将在注册前60天内接受资格筛选。筛查将包括在任何研究程序之前获得知情同意。接下来是病史、体检、对当前药物的回顾、安全实验室的血液样本(WBC、Hct、Hgb、血小板计数；化学板；HIV、人类白细胞抗原B27、乙肝病毒和丙型肝炎病毒的筛查)；女性的尿孕测试。将对粪便进行感染检测。 符合条件的志愿者将被纳入这项研究，并于第一天被GCRC录取。他们将在第0天饮用测量剂量的空肠弯曲菌，并跟踪大约9个住院日，在此期间，我们预计至少有75%的人会出现腹泻疾病，将立即使用替代液体(口服或静脉注射，根据指示)和抗生素进行治疗。在住院期间，将对受试者进行任何不良事件评估，并对血液和粪便样本进行感染标志和免疫反应标志的分析。受试者必须症状缓解或消失，两次粪便培养阴性间隔超过12小时才有资格出院，并将在第21、28、35、60和90天的门诊随访中接受进一步的AE评估以及血液和粪便分析。 8名受试者将在首次服药约98天后返回接受治疗，住院和门诊随访情况与上文相同。很少或根本没有人会患上腹泻病。四名幼稚(以前未接触过)的受试者也将在第98天接受该剂量，以确认该剂量的75%的发病率。他们将像最初的小组一样被跟踪。所有参与者将在接受最后一剂疫苗后6个月通过电话进行评估。

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. The goal of this research is to continue to develop a model of infection with Campylobacter jejuni, a bacterium that causes food and water-borne disease (mainly diarrhea). The objectives are to 1) determine if healthy subjects develop short-term (less than 6 month) protection to reinfection with C. jejuni; and 2) characterize the immune responses to C. jejuni infection. Information obtained will be used in development of a vaccine against Campylobacter infections. Volunteers will be screened for eligibility within 60 days prior to enrollment. Screening will include obtaining informed consent prior to any study procedure. This will be followed by medical history, physical examiniation, review of current medications, blood samples for safety labs (WBC, Hct, Hgb, platelet count; chemistry panel; screening for HIV, HLA-B27, HBV, and HCV); urine pregnancy testing for females. Stool will be tested for infection. Eligible volunteers will be enrolled in the study and admitted to the GCRC on Day -1. They will drink a measured dose of C. jejuni on Day 0, and followed for appoximately 9 inpatient days, during which time we expect at least 75% to develop a diarrheal illness, which will be promptly treated with replacement fluids (oral or IV, as indicated) and antibiotics. During the inpatient period, subjects will be assessed for any adverse events, and blood and stool specimens will be analyzed for markers of infection and markers of immune response. Subjects must have resolved or resolving symptoms and two negative stool cultures greater than 12 hours apart to be eligible for discharge, and will be seen in outpatient follow-up at 21, 28, 35, 60 and 90 days for additional AE assessments and blood and stool analysis. Eight subjects will return for redosing approximately 98 days after the initial dose, with the same inpatient and outpatient follow-up as above. Few or none should develop a diarrheal illness. Four naive (previously unexposed) subjects will also receive the dose on Day 98 to confirm a 75% illness rate with this dose. They will be followed as the initial group was. All participants will be assessed by phone 6 months after the final dose they received.