Background:  Here we report on the safety and immunogenicity of a preventative vaccine that consists of DNA priming and modified vaccinia virus Ankara (MVA) boosting (DNA/MVA vaccine). Both DNA and MVA components of the vaccine are single immunogens that express clade B Gag, Pol, and Env in virus like particles. Simian-human immunodeficiency virus (SHIV) and simian immunodeficiency virus (SIV) prototypes for the vaccine have provided protection against disease in SHIV and SIV non-human primate challenge models.

Methods:  In this ongoing, prospective, randomized, double-blind, placebo-controlled dose-escalation study, volunteers were vaccinated intramuscularly at months 0 and 2 with JS7 DNA and boosted at months 4 and 6 with MVA62. A low-dose group (10 vaccine recipients and 2 placebos) received 0.3 mg of DNA and 10⁷ TCID₅₀ of MVA. The high-dose group (30 vaccine recipients and 6 placebos) received 3 mg of DNA and 10⁸ TCID₅₀ of MVA. Volunteers were evaluated for safety throughout the study. Intracellular cytokine staining for responding T cells and Gag enzyme-linked immunosorbent assays (ELISA) were performed by the HVTN Laboratory Program. The Env ELISA was performed at Emory.

Results:  Both the low and high doses of the vaccine were well tolerated. Injection site pain or tenderness was either not present (33.3%) or rated as mild (50%) or moderate (16.6%). No systemic symptoms were noted in 45.8% of volunteers and the remainder had either mild (31.2%) or moderate (22.9%) symptoms. Side effects and tolerability were not significantly different between the low- and high-dose groups. Overall, T cell responses were similar in the low- and high-dose group. For the high-dose group, 75% of the volunteers had responding CD4 T cells and 37% had responding CD8 T cells. The median magnitudes of positive responses were 0.11% of total CD4 T cells and 0.15% of total CD8 T cells. For the high dose, 82% of the CD4 responders and 67% of the CD8 responders had interleukin (IL) -2 and interferon (IFN) -γ co-producing cells at the peak response. Anti-Gag and anti-Env antibody responses were more frequently seen in the high- than the low-dose group. Of the volunteers, 88% exhibited binding antibody for Env in the high-dose group; but only 22% in the low-dose group. The second MVA increased the CD8 and antibody responses, but not the CD4 responses.

Conclusions:  The majority of vaccinated participants demonstrated cellular responses at both low and high doses to this well-tolerated DNA/MVA vaccine regimen. Testing of the vaccines in additional volunteers with 3-injection regimens using a single DNA prime, or MVA-only; and planning for a phase II trial are underway.