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

Abstract 

Immunization with synthetic amyloid β-protein (Aβ) peptide has resulted in preventing and clearing Aβ 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-Aβ antibodies but also the prevention of an adverse T cell-mediated, proinflammatory autoimmune response. In this study, we developed a DNA vaccine, p(Aβ_3–10)₁₀-IL-4, encoding ten tandem repeats of Aβ_3–10 fused with mouse cytokine interleukin-4 (IL-4) as a molecular adjuvant. Wild-type mice were injected intramuscularly with p(Aβ_3–10)₁₀-IL-4 followed by in vivo electroporation. The p(Aβ_3–10)₁₀-IL-4 vaccine elicited high titer anti-Aβ antibodies which bound to Aβ plaque in brain tissue from a ten-month-old APP/PS1 transgenic mouse. The antibody isotype was mainly IgG₁ and the IgG₁/IgG_2a ratio in the p(Aβ_3–10)₁₀-IL-4 group was approximately eight times greater than that of the Aβ₄₂ group. Ex vivo cultured splenocytes isolated from mice immunized with p(Aβ_3–10)₁₀-IL-4 exhibited a low IFN-γ response and a high IL-4 response compared with the control group. These results indicate that immunization with the p(Aβ_3–10)₁₀-IL-4 vaccine induced effective anti-Aβ 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(Aβ_3–10)₁₀-IL-4, may be a safe and efficient vaccine for AD.

Keywords: Alzheimer's disease, Amyloid β-protein, DNA, Vaccine, In vivo electroporation