HIV VACCINE TRIAL CLINICAL UNIT

这项建议描述了建立艾滋病毒疫苗临床试验单位(HVTU)，这是哈佛医学院、哈佛公共卫生学院、芬威社区卫生中心和布朗大学的研究人员的共同努力。HVTU将对候选艾滋病毒疫苗进行全面整合和协调的实验室和临床评估计划，其最终目标是开发一种可在世界各地使用的安全有效的艾滋病毒疫苗。HVTU的综合资源拥有大量和多样化的患者群体，可以在国内和国际环境中进行I期、II期和III期研究。在国内，研究将在大波士顿和罗德岛地区的人口中进行；在国际上，研究将在博茨瓦纳进行，地点由哈佛公共卫生学院建立。在获奖的第一年，我们计划招收100名受试者参加第一阶段的研究，50名受试者参加第二阶段的研究，并开始招收多达600名受试者参加第三阶段或“概念测试”试验。包括对我们设计和进行第一阶段、第二阶段和第三阶段研究的方法的描述。还包括招募、挑选和保留来自低风险和高风险类别的志愿者的计划，重点是从少数族裔社区招募个人。还描述了从受试者那里获得真正知情同意的程序。将通过利用国内和博茨瓦纳国际站点的社区咨询委员会(CAB)寻求社区参与。HVTU的调查人员还拥有进行所有必要研究的实验室资源，并具有开发评估免疫原性的创新方法的广泛能力。创新研究的例子包括涉及体液免疫、细胞免疫、粘膜免疫和非人类灵长类动物研究的重要领域。作为HIV疫苗试验网络(HVTN)的一个单位，我们的HVTU计划为HVTN的科学领导做出贡献。HVTU的P.I.R.Dlin博士已被提名为HVTN科学指导委员会成员和第一/第二阶段委员会主席。多林博士还被世界卫生组织提名为“概念测试”试验的联合主席，该试验是由美国卫生与技术研究所提出的。HVTN还提名布鲁斯·沃克(Bruce Walker)博士为科学指导委员会成员，并提名布鲁斯·沃克(Bruce Walker)博士为科学指导委员会成员，同时也是联合调查员的玛丽安·纽特拉博士(Dr.Marian Netria)已被提名为粘膜免疫工作组成员，该工作组将在粘膜免疫领域为HVTN提供科学领导。包括马克斯·埃塞克斯博士、约瑟夫·索德罗斯基博士和诺曼·莱特文博士在内的HVTU的其他联合调查人员预计也将为HVTU提供重要的科学投入，并为HVTN提供国家和国际上的重要科学投入。

This proposal describes the establishment of an HIV Vaccine Clinical Trial Unit (HVTU) which is a combined effort by investigators at Harvard Medical School, Harvard School of Public Health, Fenway Community Health Center, and Brown University. The HVTU will conduct a fully integrated and coordinated program for the laboratory and clinical evaluation of candidate HIV vaccines, whose ultimate objective is the development of a safe and effective HIV vaccine, which can be used throughout the world. The combined resources of the HVTU have large and diversified patient populations with which to carry out phase I, phase II, and phase III studies in both domestic and international settings. Domestically, the studies will be carried out in populations based in the greater Boston and Rhode Island areas; internationally, studies are to be carried out in Botswana, in a site established by the Harvard School of Public Health. In the first year of the award, we plan to enroll 100 subjects in phase I studies, 50 subjects in phase II studies, and to begin enrollment of up to 600 subjects for a phase III or "test of concept" trial. Descriptions of our approach to the design and conduct of phase I, II, and III studies are included. Plans are also contained for the recruitment, selection, and retention of volunteers from lower and higher risk categories, with emphasis on recruitment of individuals from minority communities. Procedures to obtain genuinely informed consent from subjects are also described. Community involvement will be sought by the utilization of community advisory boards (CABs), both domestically and in the international site in Botswana. The investigators of the HVTU also have the laboratory resources to conduct all required studies, and have extensive capabilities for the development of innovative approaches to assessment of immunogenicity. Examples of innovative studies are included which address important areas of humoral immunity, cell mediated immunity, mucosal immunity, and studies in non-human primates. As a unit in the HIV Vaccine Trials Network (HVTN), our HVTU plans to contribute to scientific leadership of the HVTN. The P.I. of the HVTU, Dr. R. Dolin, has been proposed as a member of the Scientific Steering Committee of the HVTN and chairman of the Phase I/II committee. Dr. Dolin has also been proposed by the HVTN as co-chair of the "test of concept" trial which has been put forward by the HVTN. Dr. Bruce Walker, co-investigator of the HVTU, has also been proposed by the HVTN as a member of the Scientific Steering Committee, and Dr. Marian Neutra, also a co-investigator, has been proposed as a member of the Mucosal Immunology Working Group, which is to provide scientific leadership for the HVTN in the area of mucosal immunity. Other co- investigators of the HVTU, including Drs. Max Essex, Joseph Sodroski, and Norman Letvin, are also anticipated to provide important scientific input, both locally for the HVTU, and nationally and internationally for the HVTN.