Aβ₄₂ gene vaccination reduces brain amyloid plaque burden in transgenic mice

Objective: To demonstrate that in APPswe/PS1ΔE9 transgenic mice, gene gun mediated Aβ₄₂ gene vaccination elicits a high titer of anti-Aβ₄₂ antibodies causal of a significant reduction of Aβ₄₂ deposition in brain. Methods: Gene gun immunization is conducted with transgenic mice using the Aβ₄₂ gene in a bacterial plasmid with the pSP72-E3L-Aβ₄₂ construct. Enzyme-linked immunoabsorbent assays (ELISA) and Western blots are used to monitor anti-Aβ₄₂ antibody levels in serum and Aβ₄₂ levels in brain tissues. Enzyme-linked immunospot (ELISPOT) assays are used for detection of peripheral blood T cells to release γ-interferon. Immunofluorescence detection of Aβ₄₂ plaques and quantification of amyloid burden of brain tissue were measured and sections were analyzed with Image J (NIH) software. Results: Gene gun vaccination with the Aβ₄₂ gene resulted in high titers of anti-Aβ₄₂ antibody production of the Th2-type. Levels of Aβ₄₂ in treated transgenic mouse brain were reduced by 60-77.5%. The Mann-Whitney U-test P = 0.0286. Interpretation: We have developed a gene gun mediated Aβ₄₂ gene vaccination method that is efficient to break host Aβ₄₂ tolerance without using adjuvant and induces a Th2 immune response. Aβ₄₂ gene vaccination significantly reduces the Aβ₄₂ burden of the brain in treated APPswe/PS1ΔE9 transgenic mice with no overlap between treated and control mice.