Aβ42 gene vaccination reduces brain amyloid plaque burden in transgenic mice

Objective: To demonstrate that in APPswe/PSI Delta E9 transgenic mice, gene gun mediated A beta(42) gene vaccination elicits a high titer of anti-A beta(42) antibodies causal of a significant reduction of A beta(42) deposition in brain. Methods: Gene gun immunization is conducted with transgenic mice using the A beta(42) gene in a bacterial plasmid with the pSP72-E3L-A beta(42) construct. Enzyme-linked immunoabsorbent assays (ELISA) and Western blots are used to monitor anti-A beta(42) antibody levels in serum and A beta(42) levels in brain tissues. Enzyme-linked immunospot (ELISPOT) assays are used for detection of peripheral blood T cells to release gamma-interferon. Immunofluorescence detection of A beta(42) 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 A beta(42) gene resulted in high titers of anti-A beta(42) antibody production of the Th2-type. Levels of A beta(42) 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 A beta(42) gene vaccination method that is efficient to break host A beta(42) tolerance without using adjuvant and induces a Th2 immune response. A beta(42) gene vaccination significantly reduces the A beta(42) burden of the brain in treated APPswe/PS1 Delta E9 transgenic mice with no overlap between treated and control mice. (c) 2006 Elsevier B.V. All rights reserved.