A Phase I Clinical Trial to Evaluate the Safety and Immunogenicity of pGA2/JS7 DNA Vaccine and Recombinant Modified Vaccinia Ankara/HIV62 Vaccine in Healthy, HIV-1-Uninfected Adult Participants

Brief Summary

Detailed Description

The worldwide HIV/AIDS epidemic may only be controlled through a safe and effective vaccine that will prevent HIV infection. DNA vaccines are inexpensive to construct, easily produced in large quantities, and stable for long periods of time. Recombinant modified vaccinia Ankara vaccines have been shown to be safe in humans, and immunogenicity after administration of both vaccines has been encouraging. When used together, a more robust immunologic response was associated with DNA HIV vaccine administration followed by modified vaccinia vaccine administration, compared to using either DNA or vaccinia vaccine alone. This study will evaluate the safety and immunogenicity of an experimental DNA HIV vaccine prime, pGA/JS7, followed by a similarly structured modified vaccinia boost, MVA/HIV62, in HIV uninfected adults. Participants in this study will be recruited only in the United States. This study will be divided into 2 parts. Each participant will be involved with their part of study for 1 year. Participants in Part 1 will be randomly assigned to one of two different vaccination groups. Group 1A participants will be randomly assigned to receive either placebo or 2 lower doses of the DNA HIV vaccine (DNA) at study entry and Month 2, followed by 2 lower doses of the modified vaccinia vaccine (MVA) at Months 4 and 6. Group 1B will not enroll until safety and immunogenicity data from Group 1A have been evaluated. Group 1B participants will receive either placebo or two higher doses of DNA at study entry and Month 2, followed by two higher doses of MVA at Months 4 and 6. Enrollment into Part 2 will begin only after safety data from Part 1 are reviewed. In Part 2, participants will be randomly assigned to one of two different vaccination groups. Within each group, participants will be randomly assigned to receive some series of vaccines or placebo. Group 2A participants will receive either placebo or the maximum tolerated dose (MTD) from Part 1 of DNA at study entry and MTD of MVA at Months 2 and 6. Group 2B participants will receive MTD of MVA at study entry and Months 2 and 6. There will be 12 study visits over 12 months for Groups 1 and 2. There will be 11 study visits over 12 months for Groups 3 and 4. Medication history, a physical exam, an interview, HIV and pregnancy prevention counseling, and adverse events reporting will occur at all visits. Blood and urine collection and an electrocardiogram (ECG) will occur at selected visits.

Primary Outcomes