CLINICAL TRIAL: PHASE I EVALUATION OF A LIVE ATTENUATED DEN4 VACCINE

该子项目是利用 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。列出的机构是 中心，不一定是研究者的机构。 登革热是一种病毒，每年造成1亿例登革热病例，是几个亚洲国家儿童死亡的主要原因之一。 该病毒有两种主要的蚊子传播媒介：阿氏伊蚊和白纹伊蚊，它们负责将疾病传播给人类。 由于与这种疾病相关的全球疾病负担，开发有效的疫苗势在必行。 在全球范围内，登革热病毒每年造成大量疾病和残疾;迫切需要安全有效的疫苗。 目前研究的目的是确定一批新的登革热病毒疫苗在人类志愿者中的安全性和有效性。 本研究是一项在健康志愿者中进行的随机、安慰剂对照、双盲研究。 我们将与位于马里兰州巴尔的摩的约翰霍普金斯大学合作开展本研究。 我们在约翰霍普金斯的同事已经测试了不同批次的同一种疫苗，并发现它在人类志愿者的初步II期试验中是安全的，耐受性良好。 （Durbin等人，Am J Trop Med. Hyg.，65（5），2001：405-413）。 本研究是一项随机、安慰剂对照、双盲研究，受试者为18-50岁的健康男性和非妊娠女性志愿者，既往无黄病毒感染史。 入组资格将基于病史、体格检查、肝脏和肾脏检测、凝血研究、HIV检测、B和C型肝炎筛查、妊娠试验、既往黄病毒感染筛查和血液学筛查的结果。 将招募符合入选和排除标准的志愿者参与研究。 每个治疗组的志愿者将被随机分配接受疫苗或安慰剂。 疫苗与安慰剂的比例分别为2.5：1。 在给药当天，在审查知情同意书后，每组将通过上臂皮下注射接受疫苗或安慰剂。受试者将在疫苗接种后由GCRC的医生和护士进行监测。 在短暂的观察期后，他们将获得日记卡和温度计，并说明如何使用它们。 志愿者还将收到研究医生的联系信息，在研究期间，研究医生将每周7天、每天24小时为志愿者提供服务。 每名志愿者将在研究第2、4、6、8、10、12、14、21、28、42和180天返回GCRC，接受研究医生的简短访视和血液检查。 血液检查的目的是监测病毒血症水平、对该病毒血症作出反应的免疫学指标，并跟踪每个志愿者的肾、肝和血液学功能。 这些访视将在研究期间持续进行。

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. Dengue is a virus which is responsible for 100 million cases of dengue fever annually, and is one of the leading causes of death in children in several Asian countries. The virus has two principal mosquito vectors; Aedes ageypti and Aedes albopictus, which are responsible for transmitting disease to humans. Due to the global burden of illness associated with this disease, the development of an effective vaccine is imperative. On a global scale, the dengue virus causes a significant amount of illness and disability annually; a safe and effective vaccine is desperately needed. The aim of the current study is to determine the safety and effectiveness, in human volunteers, of a new lot of dengue virus vaccine. This study is a randomized, placebo-controlled, double-blind study in healthy volunteers. We will be conducting this study in conjunction with Johns Hopkins University in Baltimore, Maryland. Our colleagues at Johns Hopkins have already tested a different lot of this same vaccine and found it to be safe and well-tolerated in initial Phase II trials in human volunteers. (Durbin et al. Am J Trop Med. Hyg., 65(5),2001:405-413). This study is a randomized, placebo-controlled, double-blind study of healthy male and non-pregnant female volunteers 18-50 years of age with no history of a previous flavivirus infection. Eligibility for enrollment will be based on results of medical history, physical exam, liver and kidney testing, coagulation studies, HIV testing, hepatitis B and C screening, pregnancy testing, screening for previous flavivirus infection and hematology screening. Volunteers who fulfill inclusion and exclusion criteria will be recruited to participate. Volunteers in each treatment group will be randomly assigned to receive either the vaccine or placebo. The vaccine to placebo ratio will be 2.5:1 respectively. On dosing day, after review of the informed consent, each group will receive either vaccine or placebo via subcutaneous injection into their upper arm. The participants will be monitored after the vaccine by physicians and nurses at the GCRC. After a brief observation period they will be given diary cards and thermometers with instructions on how to use them. Volunteers will also receive contact information for the study doctor who will be available to them 24 hours a day 7 days a week for the duration of the study. Each volunteer will return to the GCRC on study days 2, 4, 6, 8, 10, 12, 14, 21, 28, 42 and 180 for a brief visit with the study physician and blood work. The purpose of the blood work is to monitor the level of viremia, immunologic indices in response to this viremia, and to follow kidney, liver and hematologic function in each volunteer. These visits will continue for the duration of the study.