This clinical research project is for clinical trials related to preventive HIV vaccines conducted at the VRC Clinic at the NIH Clinical Center. These consist of a screening protocol and clinical trials to evaluate candidate preventive HIV-1 vaccines including: DNA vaccine constructs, a recombinant adenoviral vector serotype 5(rAd5) vaccine, and a recombinant adenoviral vector serotype 35 (rAd35) vaccine. Studies have been designed to evaluate dose, immunogenicity, route of administration, device for administration and prime-boost regimens. A brief summary of each studies to date 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. In FY 07 a manuscript describing results through week 52 was published. The long-term follow-up required by the protocol continued and is due to be complete during FY08. ? ? VRC 006 (04-I-0128) was the first Phase I clinical trial of an investigational recombinant serotype 5 adenoviral vector (rAd5) vaccine, VRC-HIVADV014-00-VP, for the prevention of HIV infection. This 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 FY07 a manuscript describing results through week 24 was published. The 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 07 a manuscript describing study results was published. ? ? VRC 008 (05-I-0148) is a Phase I study of the prime-boost vaccination regimen consisting of 3 vaccinations with the 6-plasmid DNA vaccine followed by a boost with the rAd5 vaccine. This study evaluated 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 FY07 administration week 94 long-term follow-up evaluations were completed and analysis of the immunogenicity results were completed. Plans for publication of study results are in progress. ? ? 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. During FY07 statistical analysis of the study was completed and a manuscript of study results is being prepared.? ? 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. During FY07 statistical analysis of the study was completed and a manuscript of study results is being prepared.? ? 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. Follow-up of study participants will be ongoing during FY 08.? ? VRC 012 (07-I-0167) is a Phase I study to evaluate a novel prototype adenoviral vector serotype 35 vaccine (rAd 35-EnvA) at 109 PU, 1010 PU and 1011 PU dosages in Part I of the study and then in heterologous prime-boost schedules with an rAd5-EnvA vaccine. During FY07 the IND and protocol completed development and regulatory approval and enrollment into sequential dose groups was initiated. At the end of FY07 evaluation of the 1011 PU dosage was in progress. ? ________________________________________
