Background: Induction of a humoral response against amyloid-beta peptide may be beneficial for Alzheimer's disease (AD) patients and may alleviate the onset and progression of AD. DNA-based vaccination provides a unique alternative method of immunization for treatment and prevention of AD. Currently, the two major delivery methods used for enhancing DNA uptake and immune responses to DNA vaccines in humans are electroporation (EP) and gene gun (GG). Objective: The goal of this translational study was to evaluate the efficacy of an AD DNA epitope vaccine (DepVac) delivered intramuscularly by EP or intradermally by GG. Methods: Humoral and cellular immune responses to immunization with DepVac were evaluated by ELISA and ELISPOT, respectively. Functional activity of the antibodies was also assessed. Results: EP- and GG-mediated immunizations with DepVac induced similar anti-amyloid-beta (A beta) antibody and T cell responses. Anti-A beta antibodies bound to amyloid plaques in AD brain tissue and to toxic forms of A beta(42) peptide. Conclusion: Both delivery methods are effective at promoting potent antibodies specific for A beta. Copyright (C) 2012 S. Karger AG, Basel