A new DNA gene vaccine encoded for full-length human myelin basic protein was studied by Bar-Or and colleagues. They assessed the safety and immune modulations of the vaccine in patients with multiple sclerosis. They found that it is safe and well tolerated and provided favorable trends on brain magnetic resonance imaging and produced beneficial antigen-specific immune changes. These immune changes consisted of a marked decrease in proliferation of interferon γ–producing myelin-reactive CD4+ T cells and a reduction in titers of myelin-specific autoantibodies from cerebral spinal fluid. Editorial perspective is provided by Olaf Stüve, MD, PhD; Todd N. Eagar, PhD; Elliot M. Frohman, MD, PhD; and Petra D. Cravens, PhD.