Immunization with a new DNA vaccine for Alzheimer's disease elicited Th2 immune response in BALB/c mice by in vivo electroporation

Immunization with synthetic amyloid beta-protein (A beta) peptide has resulted in preventing and clearing A beta deposits as well as improving cognitive function in transgenic mouse models of Alzheimer's disease (AD). But similar immunization studies in humans were halted due to the risk of inducing T cell-mediated meningoencephalitis. A safe and effective vaccine for AD requires not only therapeutic levels of anti-A beta antibodies but also the prevention of an adverse T cell-mediated, proinflammatory autoimmune response. In this study, we developed a DNA vaccine, p(A beta(3-10))(10)-IL-4, encoding ten tandem repeats of A beta(3-10) fused with mouse cytokine interleukin-4 (IL-4) as a molecular adjuvant. Wild-type mice were injected intramuscularly with p(A beta(3-10))(10)-IL-4 followed by in vivo electroporation. The p(A beta(3-10))(10)-IL-4 vaccine elicited high titer anti-A beta antibodies which bound to A beta plaque in brain tissue from a ten-month-old APP/PS1 transgenic mouse. The antibody isotype was mainly IgG(1) and the IgG(1)/IgG(2) ratio in the p(A beta(3-10))(10)-IL-4 group was approximately eight times greater than that of the A beta(42) group. Ex vivo cultured splenocytes isolated from mice immunized with p(A beta(3-10))(10)-IL-4 exhibited a low IFN-gamma response and a high IL-4 response compared with the control group. These results indicate that immunization with the p(A beta(3-10))(10)-IL-4 vaccine induced effective anti-A beta antibodies and elicited a Th2-polarized immune response that had a lower potential to cause an inflammatory T cell response. Thus, the DNA vaccine, p(A beta(3-10))(10)-IL-4, may be a safe and efficient vaccine for AD. Crown Copyright (C) 2011 Published by Elsevier B.V. All rights reserved.