Safety of and Immune Response to a Prime-Boost Vaccine Regimen in HIV-Uninfected Vaccine-Naive Adults

Some of the first HIV vaccines were designed to trigger neutralizing antibody responses as a way to prevent HIV infection. Unfortunately, the first versions of these vaccines were not able to achieve their desired response. An alternative strategy to the antibody approach is the stimulation of HIV-specific CD8 T-lymphocyte (CTL) responses. CTL responses were previously demonstrated to play an important role in the control of simian immunodeficiency virus (SIV), the HIV equivalent seen in rhesus macaque monkeys. Additionally, other studies suggest CTLs play an important role in viral control during chronic infection. Based on this information, several groups have shifted their focus to the development of CTL-based vaccines, some of which have entered advanced clinical trials. A DNA/rMVA vaccine strategy is structured to bring about both T-cell and antibody responses. The primary vaccination is DNA based and will express only HIV proteins as a way to produce an HIV-focused immune response. An rMVA vaccine strategy expresses both HIV and MVA proteins and may amplify the focused response of a DNA vaccination. Participants in this study will receive either a combined DNA/rMVA vaccine strategy, in which they receive both types of vaccines; an rMVA vaccine strategy, in which they receive only the rMVA vaccine; or a placebo. The DNA and rMVA are physically two different vaccinations given at separate times, but in the DNA/rMVA group, they will be used together to make up one preventive regimen. Both vaccine components express noninfectious virus-like particles. This study is a multicenter, randomized study that is conducted in two parts and comprised of five groups. In all groups, participants will receive four injections. In Part A, Groups 1 and 2 will be compared. In Group 1, participants will receive two shots of the DNA vaccine and two shots of the rMVA vaccine. In Group 2, participants will receive four placebo injections. In Part B, Groups 3, 4, and 5 will be compared. In Group 3, the combination vaccine strategy will be used again; in Group 4, a single-vaccine strategy of three injections of the rMVA vaccine and one injection of placebo will be given; and in Group 5, participants will again receive four placebo injections. The study will last for a total of 12 months for participants, including enrollment and follow-up.