This project is for all VRC clinical trials related to preventive HIV vaccines. These currently consist of a screening protocol and several Phase I clinical trials including: a study of a 4-plasmid DNA vaccine, a study of a 6-plasmid DNA vaccine, a study of a recombinant adenoviral vector (rAd) vaccine, and four studies to evaluate DNA vaccines and rAd vaccine combined in a prime-boost regimen. A brief summary of each of these studies follow.? ? The screening protocol, VRC 000 (02-I-0127), facilitates recruitment and screening of healthy, HIV-negative subjects for investigational preventive HIV vaccine clinical trials. Educational materials on vaccines are reviewed with and provided to subjects before enrollment into a study.? ? VRC 004 (03-I-0022) was the first Phase I clinical trial of a multiclade 4-plasmid DNA vaccine, VRC-HIVDNA009-00-VP, which expresses a Gag-Pol-Nef polyprotein from clade B HIV-1 and Env glycoproteins from clades A, B and C. This study evaluated the 2 mg, 4 mg and 8 mg dosage. During FY 06 the final study analysis was completed and a manuscript describing results through week 52 accepted for publication. About half of the 5 year long-term follow-up required by the protocol is completed. ? ? VRC 006 (04-I-0128) was the first Phase I clinical trial of an investigational recombinant serotype 5 adenoviral vector (rAd5) vaccine, designated VRC-HIVADV014-00-VP, for the prevention of HIV infection. This rAd vaccine is composed of 4 adenoviral vectors (in a 3:1:1:1 ratio) that encode for the HIV-1 Gag/Pol polyprotein from clade B and HIV-1 Env glycoproteins from clades A, B, and C, respectively. This study evaluated the 109 PU, 1010 PU and 1011 PU dosages.. In FY 06 the final study analysis was completed and a manuscript describing results through week 24 was accepted for publication. The 5 year long-term follow-up required by the protocol is ongoing.? ? VRC 007 (04-I-0254) was the first Phase I clinical trial of a multiclade 6-plasmid HIV-1 DNA vaccine, VRC-HIVDNA016-00-VP, which expresses Gag, Pol and Nef proteins from clade B HIV-1 and Env glycoproteins from clades A, B and C. The 4 mg dosage was evaluated. In FY 05 study accrual, final clinical visits and immunological assays of study samples were completed. In FY 06 the final study statistical analysis was completed. ? ? VRC 008 (05-I-0148) is the first Phase I study of the complete prime-boost vaccination regimen consisting of 3 vaccinations with the 6-plasmid DNA vaccine followed by a boost with the rAd5 vaccine. This study is evaluating the safety and immunogenicity of both Biojector and needle/syringe as injection devices for the DNA vaccine, as well as safety and immunogenicity of two different dosages for the rAd5 booster. The study was designed to enroll equal numbers of subjects with low and high antibody titers to adenovirus serotype 5 at enrollment in order to gain a better understanding of whether pre-existing antibody affects the safety and immunogenicity of the rAd5 booster. During FY06 administration of study vaccinations and short-term follow-up was completed. Immunogenicity assays at key timepoints have been completed and analysis of results is ongoing. ? ? VRC 009 (05-I-0081) is a Phase I study of the rAd5 vaccine as a booster vaccination in subjects previously immunized with the 4 mg or 8 mg dose of the 4-plasmid multiclade DNA vaccine in the VRC 004 study. Ten subjects enrolled and during FY06 the planned 24 weeks of clinical and immunogenicity follow-up were completed. Statistical analysis of the study is in progress.? ? VRC 010 (05-I-0140) is a Phase I study of the rAd5 vaccine as a booster vaccination in subjects previously immunized with 4 mg of the 6-plasmid multiclade DNA vaccine in the VRC 007 study. Only a small number of subjects were eligible to participate; 4 subjects enrolled and completed the 24 weeks of follow-up. Statistical analysis of the study is in progress.? ? VRC 011 (06-I-0149) is a Phase I study of to evaluate the intramuscular, subcutaneous and intradermal routes of administration for priming vaccinations with either three injections of the 6-plasmid DNA vaccine or one injection of the rAd5 vaccine. In all schedules a rAd5 booster injection is administered IM. The study was designed to enroll 60 subjects total with equal numbers of subjects with negative and positive antibody titers to adenovirus serotype 5 at enrollment in order to gain a better understanding of whether pre-existing antibody affects the safety and immunogenicity of the regimens. During FY06 the protocol was developed, approved and opened to accrual, with over 1/3 of the target accrual completed. Enrollments are ongoing and it is expected that the study will complete accrual and the short-term follow-up through Week 52 in FY07.?
