• Safety (local and systemic reactogenicity signs and symptoms, laboratory measures, and adverse events) [ Time Frame: After each injection and for 12 months after the first injection ] [ Designated as safety issue: Yes ]
  
• Magnitude of HIV-specific T-cell responses assessed by the magnitude of IFN-gamma enzyme-linked immunosorbent spot (ELISpot) responses [ Time Frame: 4 weeks after adenoviral vaccine boost ] [ Designated as safety issue: Yes ]
  

• Titer of HIV-specific binding antibodies assessed by enzyme-linked immunosorbent assay (ELISA) [ Time Frame: 4 weeks after adenoviral vaccine boost ] [ Designated as safety issue: Yes ]
  

One factor that may affect safety and immunogenicity to an HIV vaccine is the route of vaccine administration. Administration into the skin (intradermal) or subcutaneous tissue may be more immunogenic or provide a different pattern of immune responses than administration by the intramuscular route. Previous studies with other preventive vaccines suggest that the resulting immunogenicity following intradermal or subcutaneous vaccine administration is comparable or better than immunogenicity observed following intramuscular administration. Increased immunogenicity though use of a particular route will likely result in greater demonstrated efficacy, requiring fewer or lower doses of vaccine to elicit a sufficient immune response.

The DNA HIV vaccine VRC-HIVDNA009-00-VP has shown immunogenicity in multiple clinical trials; in one trial, the DNA vaccine demonstrated a nearly 100% CD4 T-cell response rate. The adenoviral vector HIV vaccine VRC-HIVADV014-00-VP has shown immunogenicity when given intramuscularly and has appeared safe and well tolerated in prior vaccine trials in HIV uninfected adults. The DNA plasmids in both vaccines code for proteins from HIV subtypes A, B, and C. This study will evaluate the safety, immunogenicity, and tolerability to a DNA HIV vaccine, followed by an adenoviral vaccine boost given either intramuscularly, intradermally, or subcutaneously, in HIV uninfected adults.

All participants will receive three doses of the DNA vaccine intramuscularly at study entry and Months 1 and 2. Participants will be randomly assigned to one of three groups, differing by how they will receive the adenoviral vaccine boost:

• Group 1 participants will receive the vaccine boost intramuscularly at Month 6
• Group 2 participants will receive the vaccine boost intradermally at Month 6
• Group 3 participants will receive the vaccine boost subcutaneously at Month 6

This study will last 1 year. There will be 12 study visits; a physical exam, medication history, and risk reduction/pregnancy prevention compliance counseling will occur at all visits. Urine and blood collection will occur at selected visits. Participants will be asked to complete a social impact assessment at Months 2, 6, and 12 and an outside testing and belief questionnaire at Months 6 and 12. Participants will be asked to record their temperature and other side effects in a symptom log on the day of each vaccination and for 3 days thereafter to report any side effects.

NOTE: In October 2007, vaccinations with the adenoviral vaccine, VRC-HIVADV014-00-VP, were discontinued. In December 2007, vaccinations with the DNA vaccine were also discontinued. Participants will be followed for safety and immune responses at regular study visits and will be asked to continue in long term follow-up for purposes of safety surveillance to a total of 5 years following initial vaccination