title: A Novel Aβ B-Cell Epitope Vaccine (rCV01) for Alzheimer's Disease Improved Synaptic and Cognitive Functions in 3 × Tg-AD Mice.
abstract: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by a progressive amyloid-β accumulation, loss of cognitive abilities, and synaptic alterations. Given the remarkable recovery of cognition in AD models of targeting-Aβ immunotherapy, we sought to determine the molecular correlate(s) associated with improvement. We evaluated the efficacy of a recombinant chimeric 6Aβ15-T antigen formulated with alum adjuvant as a novel Aβ B-cell epitope vaccine (rCV01) in 3 × Tg-AD mice. rCV01 elicited robust Th2-polarized Aβ-specific antibodies without autoimmune T cell responses in 3 × Tg-AD mice. The long-lasting anti-Aβ42 antibodies were associated with markedly reduced AD-like pathology, enhanced synaptic function, and improved cognitive performance in aged 3 × Tg-AD mice. This is the first report to provide one hypothesis for the improved outcomes following vaccination is a reduction in the levels of active calpain in rCV01-immunized AD mice, which is likely attributable to preventing dynamin 1 and PSD-95 degradation allowing functional recovery of cognition. rCV01 is a highly immunogenic recombinant chimeric 6Aβ15-T vaccine that shows clear neuroprotective properties in preclinical mouse models of AD and is a candidate for an effective AD vaccine.
authors.affiliation: Beijing Institute of Biotechnology, 20 Dongdajie Street, Fengtai District, Beijing, 100071, China. yunzhouyu@163.com.
authors.forename: Yun-Zhou
authors.initials: YZ
authors.lastname: Yu
authors.affiliation: Beijing Institute of Biotechnology, 20 Dongdajie Street, Fengtai District, Beijing, 100071, China.
authors.forename: Si
authors.initials: S
authors.lastname: Liu
authors.affiliation: Beijing Institute of Biotechnology, 20 Dongdajie Street, Fengtai District, 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, 20 Dongdajie Street, Fengtai District, Beijing, 100071, China.
authors.forename: DanYang
authors.initials: D
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, 20 Dongdajie Street, Fengtai District, Beijing, 100071, China. amms832@126.com.
authors.forename: Xiao-Wei
authors.initials: XW
authors.lastname: Zhou
authors.affiliation: Beijing Institute of Biotechnology, 20 Dongdajie Street, Fengtai District, Beijing, 100071, China.
authors.forename: Zhi-Wei
authors.initials: ZW
authors.lastname: Sun
authors.affiliation: Institute of Life Science and Biotechnology, Beijing Jiaotong University, Beijing, 100044, China.
authors.forename: Pei-Tang
authors.initials: PT
authors.lastname: Huang
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D023582:Alzheimer Vaccines / Q000008:administration & dosage* / Q000235:genetics; D016229:Amyloid beta-Peptides / Q000008:administration & dosage* / Q000235:genetics; D000818:Animals; D003071:Cognition / Q000187:drug effects* / Q000502:physiology; D018985:Epitopes, B-Lymphocyte / Q000008:administration & dosage* / Q000235:genetics; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D013569:Synapses / Q000187:drug effects / Q000473:pathology / Q000502:physiology*
chemical_list: D023582:Alzheimer Vaccines; D016229:Amyloid beta-Peptides; D018985:Epitopes, B-Lymphocyte
keywords: Alzheimer’s disease; Amyloid-β; Dynimin 1; Immunotherapy; PSD-95; Synapses