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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01AI048023-05
Application #
6773171
Study Section
Special Emphasis Panel (ZAI1-HSD-A (M1))
Program Officer
Power, Maureen E
Project Start
2000-06-01
Project End
2008-12-31
Budget Start
2004-06-01
Budget End
2008-12-31
Support Year
5
Fiscal Year
2004
Total Cost
$2,144,184
Indirect Cost
Name
Harvard University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
047006379
City
Boston
State
MA
Country
United States
Zip Code
02115
Frey, Sharon E; Peiperl, Laurence; McElrath, M Juliana et al. (2014) Phase I/II randomized trial of safety and immunogenicity of LIPO-5 alone, ALVAC-HIV (vCP1452) alone, and ALVAC-HIV (vCP1452) prime/LIPO-5 boost in healthy, HIV-1-uninfected adult participants. Clin Vaccine Immunol 21:1589-99
Wecker, M; Gilbert, P; Russell, N et al. (2012) Phase I safety and immunogenicity evaluations of an alphavirus replicon HIV-1 subtype C gag vaccine in healthy HIV-1-uninfected adults. Clin Vaccine Immunol 19:1651-60
Walsh, Stephen R; Dolin, Raphael (2011) Vaccinia viruses: vaccines against smallpox and vectors against infectious diseases and tumors. Expert Rev Vaccines 10:1221-40
Churchyard, Gavin J; Morgan, Cecilia; Adams, Elizabeth et al. (2011) A phase IIA randomized clinical trial of a multiclade HIV-1 DNA prime followed by a multiclade rAd5 HIV-1 vaccine boost in healthy adults (HVTN204). PLoS One 6:e21225
Gorse, Geoffrey J; Baden, Lindsey R; Wecker, Margaret et al. (2008) Safety and immunogenicity of cytotoxic T-lymphocyte poly-epitope, DNA plasmid (EP HIV-1090) vaccine in healthy, human immunodeficiency virus type 1 (HIV-1)-uninfected adults. Vaccine 26:215-23
de Bruyn, Guy; Hudgens, Michael G; Sullivan, Patrick S et al. (2005) Participant retention in clinical trials of candidate HIV vaccines. J Acquir Immune Defic Syndr 39:499-501
Goepfert, Paul A; Horton, Helen; McElrath, M Juliana et al. (2005) High-dose recombinant Canarypox vaccine expressing HIV-1 protein, in seronegative human subjects. J Infect Dis 192:1249-59
Lee, Deborah; Graham, Barney S; Chiu, Ya-Lin et al. (2004) Breakthrough infections during phase 1 and 2 prime-boost HIV-1 vaccine trials with canarypox vectors (ALVAC) and booster dose of recombinant gp120 or gp160. J Infect Dis 190:903-7
de Bruyn, Guy; Rossini, Anthony J; Chiu, Ya-Lin et al. (2004) Safety profile of recombinant canarypox HIV vaccines. Vaccine 22:704-13