• Safety of vaccination, as measured by number of adverse events, local and systemic reactogenicity signs and symptoms, changes in electrocardiogram (ECG), cardiac troponin I levels, and differences in other safety laboratory measures [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
  

• HIV-specific intracellular cytokine staining (ICS) assay and/or interferon-gamma ELISA responses [ Time Frame: At 2 weeks following the third and fourth injection ] [ Designated as safety issue: No ]
  
• Vaccinia-specific neutralizing binding assays performed on serum samples from participants receiving the MVA vaccine [ Time Frame: At 2 weeks following the final vaccination ] [ Designated as safety issue: No ]
  
• Self reports on social impact of participation in study [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  

The worldwide HIV/AIDS epidemic may only be controlled through the development of a safe and effective vaccine that will prevent HIV infection. DNA-based vaccines alone promote a weak immune response but when used as priming immunogens, followed by a recombinant viral vaccine that is a very attenuated vaccinia (smallpox) vaccine presenting the same immunogens as a booster, immunization with such a combination regimen seems to induce much stronger responses. EP-1233 is a DNA-HIV-recombinant vaccine designed to interact with CD4 (helper-inducer) and CD8 (cytotoxic) T lymphocytes (T cells) to prime CD4 and CD8 cells to respond to HIV components. MVA-mBN32 is a HIV-recombinant viral (MVA) vaccine that through other ways of interacting with CD4 and CD8 cells to immunize (boost) with similar HIV immunogens, may result in a stronger immune response.

The purpose of this study is to determine the safety of and immune response to two experimental vaccines for the prevention of HIV infection, individually and in combination, in healthy adults who have not been previously vaccinated against smallpox. Participants will be randomly assigned to one of three groups. All participants will receive injections at Days 0, 28, 84, and 168 of the study. Participants assigned to Group 1 will receive, on Day 0, one injection in each arm of EP-1233 or placebo and the same study product (EP-1233 or the DNA placebo) on Day 28. Thereafter, each Group 1 participant will receive one injection of MVA-mBN32 or placebo on Days 84 and 168. Groups 2 and 3 will not begin enrollment until safety and immunogenicity data from Group 1 have been evaluated. Participants assigned to Group 2 will receive only the DNA vaccine EP-1233 (or placebo) in each arm on all injection days. Participants in Group 3 will not begin enrollment until safety and immunogenicity data from Group 1 have been evaluated. Participants assigned to Group 3 will receive a consistent regimen of MVA-mBN32 (or placebo) on all injection days. Participants will be required to keep a symptom log for 3 days after each injection and attend clinical visits on Day 0, 14, 28, 42, 84, 98, 168, 182, 273, and 364 of the study. At each of the 10 visits, a physical exam, cardiac assessment, and HIV risk reduction and prevention counseling will occur. Blood collection will occur on Days 0, 14, 42, 98, 182, 273, and 364. Urine collection will occur on Days 14, 42, 98, and 182.