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.
