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Amyloid β3-10 DNA vaccination suggests a potential new treatment for Alzheimer's disease in BALB/c mice

XING Xiao-na ZHANG Wei-ge SHA Sha LI Yu GUO Rong WANG Cai CAO Yun-peng

中华医学杂志(英文版)2011,Vol.124Issue(17):2636-2641,6.
中华医学杂志(英文版)2011,Vol.124Issue(17):2636-2641,6.DOI:10.3760/cma.j.issn.0366-6999.2011.17.013

Amyloid β3-10 DNA vaccination suggests a potential new treatment for Alzheimer's disease in BALB/c mice

Amyloid β3-10 DNA vaccination suggests a potential new treatment for Alzheimer's disease in BALB/c mice

XING Xiao-na 1ZHANG Wei-ge 1SHA Sha 1LI Yu 1GUO Rong 1WANG Cai 1CAO Yun-peng1

作者信息

  • 1. Department of Neurology,First Affiliated Hospital of China Medical University,Shenyang,Liaoning 110001,China
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摘要

Abstract

Background Amyloid β1-42 (Aβ42) peptide vaccination has been proved to be effective in reducing amyloid burden in brain and improving cognitive function in Alzheimer's disease (AD) mouse models.But the phase Ⅱ trial of Aβ42 peptide vaccine was halted because of T cell-mediated meningoencephalitis.In this study,a DNA vaccine,p(Aβ3-10)10-CpG,was constructed to test whether it would induce predominant TH2 immune response upon immunization of BALB/c mice.Methods BALB/c mice were vaccinated intramuscularly with p(Aβ3-10)10-CpG plasmids.Aβ42 peptide,pcDNA3.1(+)empty vector and PBS were injected to the control groups.Expression of interesting gene in injected muscle was identified by immunohistochemistry.Anti-Al3 antibody titers,isotype profiles as well as cytokines in ex vivo splenocytes culture supernatants were analyzed by enzyme-linked immunosorbent assay (ELISA).Results P(Aβ3-10)10-CpG plasmid was expressed in muscle after injection detected by immunohistochemistry.The p(Aβ3-10)10-CpG vaccine induced high titers of anti-Aβ antibodies in BALB/c mice.And isotype of the antibodies was mainly IgG1,the IgG1/IgG2a ratio for the p(Aβ3-10)10-CpG group was approximately 5 times greater than that for the Aβ42 peptide group.Ex vivo cultured splenocytes isolated from mice immunized with p(Aβ3-10)10-CpG exhibited high interleukin-4 response and low interleukin-Y (IFN-Y) response.Conclusions Immunization with p(Aβ3-10)10-CpG vaccine primarily induces a TH2 type of response,thus reduces the probability of inflammation.This p(Aβ3-10)10-CpG vaccine possesses the basic factors required for a safe and effective AD vaccine.

关键词

Alzheimer's disease/vaccine/DNA

Key words

Alzheimer's disease/vaccine/DNA

引用本文复制引用

XING Xiao-na,ZHANG Wei-ge,SHA Sha,LI Yu,GUO Rong,WANG Cai,CAO Yun-peng..Amyloid β3-10 DNA vaccination suggests a potential new treatment for Alzheimer's disease in BALB/c mice[J].中华医学杂志(英文版),2011,124(17):2636-2641,6.

基金项目

This study was supported by a grant of the National Natural Science Foundation of China (No.30471927). (No.30471927)

中华医学杂志(英文版)

OACSCDCSTPCDMEDLINESCI

0366-6999

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