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

• Published in: Clinical immunology (Orlando, Fla.) Fla.), 2013-10, Vol.149 (1), p.11-24
• Main Authors: Yu, Yun-Zhou, Wang, Shuang, Bai, Jie-Ying, Zhao, Meng, Chen, Ao, Wang, Wen-Bin, Chang, Qing, Liu, Si, Qiu, Wei-Yi, Pang, Xiao-Bin, Xu, Qing, Sun, Zhi-Wei
• Format: Article
• Language: English
• Subjects: Allergy and Immunology; Alzheimer Disease - immunology; Alzheimer Disease - psychology; Alzheimer Disease - therapy; Alzheimer Vaccines - administration & dosage; Alzheimer's disease; Amyloid beta-Peptides - genetics; Amyloid beta-Peptides - immunology; Animals; Carrier protein; DNA vaccine; Epitopes - immunology; Female; Immunoglobulin G - blood; Immunoglobulin G - immunology; Immunotherapy; Interferon-gamma - immunology; Interleukin-4 - immunology; Malaria Vaccines - immunology; Maze Learning; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Transgenic; Peptide Fragments - genetics; Peptide Fragments - immunology; T-Lymphocytes - immunology; Toxin fragment; Vaccines, DNA - administration & dosage
• ISSN: 1521-6616; 1521-7035
• DOI: 10.1016/j.clim.2013.05.016

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.