Evaluating the Immune Response to a rAd5 HIV Vaccine Administered in Three Different Ways in Healthy, HIV-Uninfected Adults

The VRC rAd5 HIV vaccine contains four different components. In this study, researchers will examine how the immune system responds to the vaccine when the four components are administered in three different ways: 1. The vaccine dose containing all four components is given as a single injection in one arm, and placebo injections are given in the other arm and both legs. 2. The vaccine dose containing all four components is divided into fourths, and one-fourth of the full dose is given in each arm and leg. 3. The four vaccine components are separated, and a different component is given in each arm and leg. This study will enroll healthy, HIV-uninfected adults. Participants will be randomly assigned to one of three groups. Group 1 will receive the entire dose of vaccine in their right arm and placebo vaccine in the other arm and both legs. Group 2 will receive all four different components of the vaccine, given separately as a different component per each arm and leg. Group 3 will receive the entire vaccine dose divided into fourths, with one fourth of the full dose given in each arm and leg. At a baseline study visit, participants will undergo a physical examination and a medical and medication history review. Female participants will also take a pregnancy test. Participants will complete questionnaires and receive counseling on HIV risk reduction and pregnancy prevention. All participants will then receive vaccine given as four injections-one each in their right arm, left arm, right thigh, and left thigh (except for Group 1, placebo injections are given in left arm and both legs). After receiving the vaccine, participants will remain in the clinic for at least 30 minutes for observation and monitoring of side effects. For 7 days after the vaccination, participants will record any side effects in a symptom log; for the first 3 days after the vaccination, study staff will call participants to ensure they are completing the symptom log. Follow-up visits will occur at Months 1, 4, and 7. These visits will include the baseline study procedures and a blood collection. Participants will be contacted by study researchers once a year for 5 years for follow-up health monitoring. Blood collected during study visits will be saved for future testing.