The purpose of this study is to determine the safety of and immune response to an experimental DNA HIV vaccine followed by boosting with either an experimental adenoviral vector HIV vaccine of serotype 5 or 35 in HIV uninfected adults. This study will also determine the safety of and immune response to an adenoviral vector HIV vaccine of serotype 5 followed by a booster of an adenoviral vector of serotype 35, or vice versa, in HIV uninfected adults.

The worldwide HIV/AIDS epidemic may only be controlled through development and utilization of a safe and effective vaccine that will prevent HIV infection. Vaccines using a DNA plasmid to prime the response to an adenoviral vector boost are currently being developed. Due to high prevalence of pre-existing immunity to adenovirus serotype Ad5 in the developing world, this study will evaluate boosting with a different serotype, Ad35, as compared to boosting with the Ad5 serotype. This study will also test the effect of the order of administration of recombinant adenoviral vector HIV vaccines when administered without the DNA plasmid vaccine. Two arms of this study will evaluate the safety and immunogenicity of the experimental multiclade, multigene HIV DNA vaccine VRC-HIVDNA044-00-VP, followed by a similarly structured adenovirus vector vaccine boost (either VRC-HIVADV027-00-VP or VRC-HIVADV038-00-VP), in HIV uninfected adults. To determine the effect of pre-existing Ad5 or Ad35 immunity, the other two arms will test the safety and immunogenicity of receiving either VRC-HIVADV027-00-VP followed by VRC-HIVADV038-00-VP, or vice versa.

Each volunteer will participate in the study for at least 6 months. Participants will be randomly assigned to one of four groups and will receive either an experimental vaccine or placebo at each vaccination visit. Group 1 participants will receive an injection of the adenoviral vector vaccine VRC-HIVADV027-00-VP at study entry and an injection of VRC-HIVADV038-00-VP at Month 3. Group 2 participants will receive an injection of the adenoviral vector vaccine VRC-HIVADV038-00-VP at study entry and an injection of VRC-HIVADV027-00-VP at Month 3. Group 3 participants will receive an injection of the VRC-HIVDNA044-00-VP vaccine at study entry and Months 1 and 2, followed by an injection of VRC-HIVADV027-00-VP at Month 6. Group 4 participants will receive an injection of the DNA HIV vaccine at study entry and Months 1 and 2, followed by an injection of VRC-HIVADV038-00-VP at Month 6.

For Groups 1 and 2, there will be 9 study visits. For Groups 3 and 4, there will be 13 study visits. Medication history, assessment of intercurrent illness and adverse effects, and HIV and pregnancy prevention counseling will occur at all visits. A medical history, a physical exam, HIV testing and counseling and blood and urine collection will occur at selected visits. Participants will also be asked to complete social impact and HIV testing and history questionnaires at selected visits.

As of 11/19/07 enrollment and vaccinations have been discontinued. Participants who have already been enrolled have been told which vaccinations they received and will be followed for a total of 5 years.

Inclusion Criteria:

• HIV-1 and -2 uninfected
• Have access to a participating HIV Vaccine Trials Unit (HVTU) and willing to be followed for the duration of the study
• Willing to receive HIV test results
• Good general health
• Pre-existing adenovirus 5 (Ad5) neutralizing antibody titer of 1:1000 ratio or greater
• Willing to use acceptable forms of contraception from at least 21 days prior to enrollment through the duration of the study

Exclusion Criteria:

• HIV vaccines in prior HIV vaccine trial
• Immunosuppressive medications within 168 days prior to first study vaccine administration
• Blood products within 120 days prior to first study vaccine administration
• Immunoglobulin within 60 days prior to first study vaccine administration
• Live attenuated vaccines within 30 days prior to first study vaccine administration
• Investigational research agents within 30 days prior to first study vaccine administration
• Subunit or killed vaccines within 14 days prior to first study vaccine administration
• Current anti-tuberculosis prophylaxis or therapy
• Clinically significant medical condition, abnormal physical exam findings, abnormal laboratory results, or past medical history that may affect current health. More information about this criterion can be found in the protocol.
• Any medical, psychiatric, or social condition that would interfere with the study.
• Serious adverse reaction to vaccines. Participants who have had an adverse reaction to pertussis vaccine as a child are not excluded.
• Autoimmune disease or immunodeficiency
• Active syphilis infection. Participants with fully treated syphilis at least 6 months prior to study entry are not excluded.
• Unstable asthma. More information about this criterion can be found in the protocol.
• Diabetes mellitus type 1 or 2. Participants with a history of isolated gestational diabetes are not excluded.
• Absence of thyroid or thyroid disease requiring treatment
• Serious angioedema within the past 3 years or requiring medication within 2 years of study entry
• Body mass index (BMI) of 40 or less OR BMI of 35 or less if certain other criteria apply. More information about these criteria can be found in the protocol.
• Uncontrolled hypertension
• Bleeding disorder
• Cancer. Participants with surgically removed cancer that is unlikely to recur are not excluded.
• Seizure disorder
• Absence of spleen
• Certain abnormal laboratory values
• Mental illness that would interfere with compliance with the protocol
• Other conditions that, in the judgment of the investigator, would interfere with the study
• Pregnant or breastfeeding