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Alzheimer's Research & Therapy
Published in: Alzheimer's Research & Therapy 1/2017

Open Access 01-12-2017 | Research article

A vaccine with Aβ oligomer-specific mimotope attenuates cognitive deficits and brain pathologies in transgenic mice with Alzheimer’s disease

Authors: Shao-wei Wang, Dong-qun Liu, Ling-xiao Zhang, Mei Ji, Yang-xin Zhang, Quan-xiu Dong, Shu-ying Liu, Xi-xiu Xie, Rui-tian Liu

Published in: Alzheimer's Research & Therapy | Issue 1/2017

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Abstract

Background

β-Amyloid peptide (Aβ) oligomers are initial factors used to induce Alzheimer’s disease (AD) development, and Aβ monomers have normal physiological function. The antibodies or vaccines against Aβ monomers have serious problems, such as side effects and low curative effects. Therefore, it is essential to specifically target Aβ oligomers rather than monomers for the treatment of AD.

Methods

The mimotopes of Aβ oligomers were obtained by panning the phage-displayed random peptide libraries using oligomer-specific antibodies as targets and expressed on the surface of EBY100 Saccharomyces cerevisiae to generate yeast cell base vaccines. One vaccine (AOE1) induced antibodies specifically against Aβ oligomers and was selected for further study. The APP/PS1 mice were subcutaneously immunized with AOE1 eight times. The levels and characteristics of antibodies induced by AOE1 were determined by enzyme-linked immunosorbent assay. The effect of AOE1 on the cognitive deficits of AD mice was tested by novel object recognition (NOR) and Y-maze. Dot blot analysis, Western blot analysis, and immunohistochemistry were applied to measure the effects of AOE1 on Aβ pathologies, neuroinflammation, and microhemorrhages in the brains of AD mice.

Results

Eight mimotope candidates of Aβ oligomers were selected and expressed on EBY100 S. cerevisiae. Only AOE1 vaccine containing mimotope L2 induced antibodies that specifically recognized Aβ42 oligomers rather than monomers. AOE1 immunization significantly increased the AD mice’s exploration times for the novel object in the NOR test and the choices for new arms in the Y-maze test, and it reduced levels of Aβ oligomers and glial activation in the AD mouse brains. No activation of Aβ-specific T cells and microhemorrhages was observed in their brains following AOE1 vaccination.

Conclusions

AOE1 is the first vaccine applying the oligomer-specific mimotope as an immunogen, which could induce antibodies with high specificity to Aβ oligomers. AOE1 immunization attenuated Aβ pathologies and cognitive deficits in AD mice, decreased the overactivation of glial cells, and did not induce microhemorrhage in the brains of AD mice. These findings suggest that AOE1 may be a safer and more effective vaccine for AD treatment.
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Metadata
Title
A vaccine with Aβ oligomer-specific mimotope attenuates cognitive deficits and brain pathologies in transgenic mice with Alzheimer’s disease
Authors
Shao-wei Wang
Dong-qun Liu
Ling-xiao Zhang
Mei Ji
Yang-xin Zhang
Quan-xiu Dong
Shu-ying Liu
Xi-xiu Xie
Rui-tian Liu
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Alzheimer's Research & Therapy / Issue 1/2017
Electronic ISSN: 1758-9193
DOI
https://doi.org/10.1186/s13195-017-0267-5

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