Effective DNA epitope chimeric vaccines for Alzheimer's disease using a toxin-derived carrier protein as a molecular adjuvant

Abstract

Active amyloid-beta (Aβ) immunotherapy is under investigation to prevent or treat Alzheimer disease (AD). We describe here the immunological characterization and protective effect of DNA epitope chimeric vaccines using 6 copies of Aβ1-15 fused with PADRE or toxin-derived carriers. These naked 6Aβ15-T-Hc chimeric DNA vaccines were demonstrated to induce robust anti-Aβ antibodies that could recognize Aβ oligomers and inhibit Aβ oligomer-mediated neurotoxicity, result in the reduction of cerebral Aβ load and Aβ oligomers, and improve cognitive function in AD mice, but did not stimulate Aβ-specific T cell responses. Notably, toxin-derived carriers as molecular adjuvants were able to substantially promote immune responses, overcome Aβ-associated hypo-responsiveness, and elicit long-term Aβ-specific antibody response in 6Aβ15-T-Hc-immunized AD mice. These findings suggest that our 6Aβ15-T-Hc DNA chimeric vaccines can be used as a safe and effective strategy for AD immunotherapy, and toxin-derived carrier proteins are effective molecular adjuvants of DNA epitope vaccines for Alzheimer's disease.