A novel Aβ B-cell epitope vaccine (rCV01) for Alzheimer's disease improved synaptic and cognitive functions in 3×Tg-AD mice


BIBLIOGRAPHIC THERAPEUTIC AGENT ANIMAL MODEL EXPERIMENTAL DESIGN OUTCOMES

Bibliographic

Year of Publication:
2016
Contact PI Name:
Yun-Zhou Yu
Contact PI Affiliation:
Beijing Institute of Biotechnology, Beijing, China
Co-Authors:
Si Liu, Hai-Chao Wang, DanYang Shi, Qing Xu, Xiao-Wei Zhou, Zhi-Wei Sun, Pei-Tang Huang
Primary Reference (PubMED ID):
Funding Source:
Natural Science Foundation of Beijing
National Science and Technology Major Project of China
Study Goal and Principal Findings:

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, in this studie was sought to determine the molecular correlate(s) associated with improvement. Was 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.

Therapeutic Agent

Therapeutic Information:
Therapy Type:
Biologic - Immunotherapy(active)
Therapeutic Agent:
Aβ B-Cell Epitope Vaccine (rCV01)
Therapeutic Target:
beta Amyloid Peptide

Animal Model

Model Information:
Species:
Mouse
Model Type:
APPxPS1xTau
Strain/Genetic Background:
Not Reported

Experimental Design

Is the following information reported in the study?:
Power/Sample Size Calculation
Randomized into Groups
Blinded for Treatment
Blinded for Outcome Measures
Pharmacokinetic Measures
Pharmacodynamic Measures
Toxicology Measures
ADME Measures
Biomarkers
Dose
Formulation
Route of Delivery
Duration of Treatment
Frequency of Administration
Age of Animal at the Beginning of Treatment
Age of Animal at the End of Treatment
Sex as a Biological Variable
Study Balanced for Sex as a Biological Variable
Number of Premature Deaths
Number of Excluded Animals
Statistical Plan
Genetic Background
Inclusion/Exclusion Criteria Included
Conflict of Interest

Outcomes

Outcome Measured
Outcome Parameters
Behavioral
Morris Water Maze
Histopathology
beta Amyloid Load
Tau Pathology
Biochemical
Brain-beta Amyloid Peptide 42
Dynamin 1
Interleukin 4 (IL-4)
Interferon (IFN) gamma
Postsynaptic Density Protein 95 (PSD95)
Spectrin
Brain-Buffer Soluble beta Amyloid Peptide 42
Brain-Buffer Insoluble beta Amyloid Peptide 42
Brain-Guanidine Soluble beta Amyloid Peptide 42
Brain-Buffer Soluble Tau Protein
Brain-Buffer Insoluble Tau Protein
Brain-beta Amyloid Oligomers
Total Tau Protein
Immunochemistry
beta Amyloid Load
Tau Protein
Immunology
Anti-beta Amyloid Antibody Titers
Epitope Mapping
Interferon (IFN) gamma Production
Splenocyte Response
T Cell Response
Pharmacodynamics
Target Engagement (Reduction beta Amyloid Peptides-Brain)
Outcomes Notes:
Note - A splenocyte can be any one of the different white blood cell types as long as it is situated in the spleen or purified from splenic tissue.

Source URL: http://alzped.nia.nih.gov/novel-aβ-b-cell-epitope