title: Co-immunization with DNA and protein mixture: a safe and efficacious immunotherapeutic strategy for Alzheimer's disease in PDAPP mice.
abstract: Active immunotherapy targeting β-amyloid (Aβ) is the most promising strategy to prevent or treat Alzheimer's disease (AD). Based on pre-clinical studies and clinical trials, a safe and effective AD vaccine requires a delicate balance between providing therapeutically adequate anti-Aβ antibodies and eliminating or suppressing unwanted adverse T cell-mediated inflammatory reactions. We describe here the immunological characterization and protective efficacy of co-immunization with a 6Aβ15-T DNA and protein mixture without adjuvant as an AD immunotherapeutic strategy. Impressively, this co-immunization induced robust Th2-polarized Aβ-specific antibodies while simultaneously suppressed unwanted inflammatory T cell reactions and avoiding Aβ42-specific T cell-mediated autoimmune responses in immunized mice. Co-immunization with the DNA + protein vaccine could overcome Aβ42-associated hypo-responsiveness and elicit long-term Aβ-specific antibody responses, which helped to maintain antibody-mediated clearance of amyloid and accordingly alleviated AD symptoms in co-immunized PDAPP mice. Our DNA and protein combined vaccine, which could induce an anti-inflammatory Th2 immune response with high level Aβ-specific antibodies and low level IFN-γ production, also demonstrated the capacity to inhibit amyloid accumulation and prevent cognitive dysfunction. Hence, co-immunization with antigen-matched DNA and protein may represent a novel and efficacious strategy for AD immunotherapy to eliminate T cell inflammatory reactions while retaining high level antibody responses.
authors.affiliation: Beijing Institute of Biotechnology, Beijing, China 100071.
authors.forename: Si
authors.initials: S
authors.lastname: Liu
authors.affiliation: Beijing Institute of Biotechnology, Beijing, China 100071.
authors.forename: DanYang
authors.initials: D
authors.lastname: Shi
authors.affiliation: Institute of Life Science and Biotechnology, Beijing Jiaotong University, Beijing, China, 100044.
authors.forename: Hai-Chao
authors.initials: HC
authors.lastname: Wang
authors.affiliation: Beijing Institute of Biotechnology, Beijing, China 100071.
authors.forename: Yun-Zhou
authors.initials: YZ
authors.lastname: Yu
authors.affiliation: Institute of Life Science and Biotechnology, Beijing Jiaotong University, Beijing, China, 100044.
authors.forename: Qing
authors.initials: Q
authors.lastname: Xu
authors.affiliation: Beijing Institute of Biotechnology, Beijing, China 100071.
authors.forename: Zhi-Wei
authors.initials: ZW
authors.lastname: Sun
mesh_terms: D000544:Alzheimer Disease / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D016229:Amyloid beta-Peptides / Q000276:immunology*; D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D000918:Antibody Specificity / Q000276:immunology; D001921:Brain / Q000473:pathology / Q000503:physiopathology; D016764:Cell Polarity; D003072:Cognition Disorders / Q000150:complications / Q000503:physiopathology / Q000628:therapy; D004195:Disease Models, Animal; D007114:Immunization; D007074:Immunoglobulin G / Q000276:immunology; D007167:Immunotherapy; D007249:Inflammation / Q000473:pathology; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D058225:Plaque, Amyloid / Q000473:pathology; D065852:Spatial Memory; D018418:Th2 Cells / Q000276:immunology; D019444:Vaccines, DNA / Q000276:immunology*
chemical_list: D016229:Amyloid beta-Peptides; D007074:Immunoglobulin G; D019444:Vaccines, DNA