Safety of and Immune Response to Two Different HIV Vaccines, Each Followed by a Adenoviral Vaccine Boost, in HIV Uninfected Adults

• Safety (local and systemic reactogenicity signs and symptoms, laboratory measures, and adverse and serious experiences) [ Time Frame: After each injection and for 6 months after the last injection ] [ Designated as safety issue: Yes ]
  
• Magnitude of HIV-specific CD4+ and CD8+ T-cell responses, defined as percentage of T cells expressing IFN-gamma or IL-2 to vaccine peptide pools [ Time Frame: Within first 6 weeks following primary adenoviral vaccination, the second DNA vaccination, and the booster adenoviral vaccination ] [ Designated as safety issue: No ]
  
• Social impact (negative experiences or problems associated with participation in the study and other social, travel, work, school, health care, life insurance, health insurance, housing, military, or other impacts identified by the participant) [ Time Frame: Throughout the study ] [ Designated as safety issue: No ]
  

• Expression of HIV-specific T-cell memory differentiation markers and other markers of interest by flow cytometry [ Time Frame: Within first 6 weeks following primary adenoviral vaccination, the second DNA vaccination, and the booster adenoviral vaccination ] [ Designated as safety issue: No ]
  
• Titer to HIV-specific binding antibodies assessed by ELISA [ Time Frame: Within first 6 weeks following primary adenoviral vaccination, the second DNA vaccination, and the booster adenoviral vaccination ] [ Designated as safety issue: No ]
  
• Titer of HIV-specific neutralization antibodies assessed by neutralizing antibody assay, if indicated [ Time Frame: Within first 6 weeks following primary adenoviral vaccination, the second DNA vaccination, and the booster adenoviral vaccination ] [ Designated as safety issue: No ]
  

Evaluating the immunogenicity of HIV vaccines is critical to improving vaccine design and development. The adenoviral vector HIV vaccine VRC-HIVADV014-00-VP has shown immunogenicity in early studies and appeared safe and well tolerated at three different doses in a prior dose-escalation vaccine trial in HIV uninfected adults. 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 DNA plasmids in both vaccines code for proteins from HIV subtypes A, B, and C, which together represent 90% of new HIV infections. This study will determine the safety and immune response to the administration of an adenoviral vector HIV vaccine or a DNA HIV vaccine, each followed by an adenoviral vaccine boost, in HIV uninfected adults.

This study will last 1 year. Participants will be randomly assigned to one of two groups. Within each group, participants will be randomly assigned to receive either vaccine or control injections. Group 1 participants will receive either placebo or the adenoviral HIV vaccine at study entry and Month 6. Group 2 participants will receive either placebo or the DNA HIV vaccine at study entry and Month 1 and the adenoviral HIV vaccine at Month 6. Participants will be asked to record their temperatures and other side effects in a symptom log on the day of each vaccination and for 3 days thereafter to report any side effects.

Group 1 participants will have 16 study visits, and a physical exam and HIV and pregnancy prevention counseling will occur at each visit. Participants will also be asked about any side effects and medications they are taking. Blood collection will occur at most visits. Urine collection will occur at selected visits. Participants will be asked to complete a social impact assessment at Months 2, 6, and 12 and a testing and belief questionnaire at Months 6 and 12.