title: 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.
authors.affiliation: Beijing Institute of Biotechnology, Beijing, China. Electronic address: yunzhouyu@163.com.
authors.forename: Yun-Zhou
authors.initials: YZ
authors.lastname: Yu
authors.forename: Shuang
authors.initials: S
authors.lastname: Wang
authors.forename: Jie-Ying
authors.initials: JY
authors.lastname: Bai
authors.forename: Meng
authors.initials: M
authors.lastname: Zhao
authors.forename: Ao
authors.initials: A
authors.lastname: Chen
authors.forename: Wen-Bin
authors.initials: WB
authors.lastname: Wang
authors.forename: Qing
authors.initials: Q
authors.lastname: Chang
authors.forename: Si
authors.initials: S
authors.lastname: Liu
authors.forename: Wei-Yi
authors.initials: WY
authors.lastname: Qiu
authors.forename: Xiao-Bin
authors.initials: XB
authors.lastname: Pang
authors.forename: Qing
authors.initials: Q
authors.lastname: Xu
authors.forename: Zhi-Wei
authors.initials: ZW
authors.lastname: Sun
mesh_terms: D000544:Alzheimer Disease / Q000276:immunology / Q000523:psychology / Q000628:therapy; D023582:Alzheimer Vaccines / Q000008:administration & dosage*; D016229:Amyloid beta-Peptides / Q000235:genetics / Q000276:immunology*; D000818:Animals; D000939:Epitopes / Q000276:immunology*; D005260:Female; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007167:Immunotherapy; D007371:Interferon-gamma / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D017780:Malaria Vaccines / Q000276:immunology; D018782:Maze Learning; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage*
chemical_list: D023582:Alzheimer Vaccines; D016229:Amyloid beta-Peptides; D000939:Epitopes; D007074:Immunoglobulin G; D017780:Malaria Vaccines; C401223:PADRE 45; D010446:Peptide Fragments; D019444:Vaccines, DNA; C480626:amyloid beta-protein (1-15); C075222:amyloid beta-protein (1-42); D015847:Interleukin-4; D007371:Interferon-gamma
keywords: Alzheimer's disease; Carrier protein; DNA vaccine; Immunotherapy; Toxin fragment