title: A novel recombinant 6Aβ15-THc-C chimeric vaccine (rCV02) mitigates Alzheimer's disease-like pathology, cognitive decline and synaptic loss in aged 3 × Tg-AD mice.
abstract: Alzheimer's disease (AD) is a neurodegenerative disorder that impairs memory and cognition. Targeting amyloid-β (Aβ) may be currently the most promising immunotherapeutic strategy for AD. In this study, a recombinant chimeric 6Aβ15-THc-C immunogen was formulated with alum adjuvant as a novel Aβ B-cell epitope candidate vaccine (rCV02) for AD. We examined its efficacy in preventing the cognitive deficit and synaptic impairment in 3 × Tg-AD mice. Using a toxin-derived carrier protein, the rCV02 vaccine elicited robust Aβ-specific antibodies that markedly reduced AD-like pathology and improved behavioral performance in 3 × Tg-AD mice. Along with the behavioral improvement in aged 3 × Tg-AD mice, rCV02 significantly decreased calpain activation concurrent with reduced soluble Aβ or oligomeric forms of Aβ, probably by preventing dynamin 1 and PSD-95 degradation. Our data support the hypothesis that reducing Aβ levels in rCV02-immunized AD mice increases the levels of presynaptic dynamin 1 and postsynaptic PSD-95 allowing functional recovery of cognition. In conclusion, this novel and highly immunogenic rCV02 shows promise as a new candidate prophylactic vaccine for AD and may be useful for generating rapid and strong Aβ-specific antibodies in AD patients with pre-existing memory Th cells generated after immunization with conventional tetanus toxoid vaccine.
authors.affiliation: Beijing Institute of Biotechnology, Beijing 100071, China.
authors.forename: Yun-Zhou
authors.initials: YZ
authors.lastname: Yu
authors.affiliation: Beijing Institute of Biotechnology, Beijing 100071, China.
authors.forename: Si
authors.initials: S
authors.lastname: Liu
authors.affiliation: Beijing Institute of Biotechnology, Beijing 100071, China.|Institute of Life Science and Biotechnology, Beijing Jiaotong University, Beijing 100044, China.
authors.forename: Hai-Chao
authors.initials: HC
authors.lastname: Wang
authors.affiliation: Beijing Institute of Biotechnology, Beijing 100071, China.
authors.forename: Dan-Yang
authors.initials: DY
authors.lastname: Shi
authors.affiliation: Institute of Life Science and Biotechnology, Beijing Jiaotong University, Beijing 100044, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Xu
authors.affiliation: Beijing Institute of Biotechnology, Beijing 100071, China.
authors.forename: Xiao-Wei
authors.initials: XW
authors.lastname: Zhou
authors.affiliation: Beijing Institute of Biotechnology, Beijing 100071, China.
authors.forename: Zhi-Wei
authors.initials: ZW
authors.lastname: Sun
authors.affiliation: Beijing Institute of Biotechnology, Beijing 100071, China.
authors.forename: Pei-Tang
authors.initials: PT
authors.lastname: Huang
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D023582:Alzheimer Vaccines / Q000008:administration & dosage* / Q000494:pharmacology; D016229:Amyloid beta-Peptides / Q000187:drug effects*; D000818:Animals; D002154:Calpain / Q000378:metabolism; D003071:Cognition / Q000187:drug effects*; D004195:Disease Models, Animal; D000076122:Disks Large Homolog 4 Protein / Q000378:metabolism; D034284:Dynamin I / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D051379:Mice; D008822:Mice, Transgenic; D014614:Vaccines, Synthetic
chemical_list: D023582:Alzheimer Vaccines; D016229:Amyloid beta-Peptides; D000076122:Disks Large Homolog 4 Protein; C501447:Dlg4 protein, mouse; D014614:Vaccines, Synthetic; D002154:Calpain; D034284:Dynamin I