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Delivery of a DNA vaccine for Alzheimer's disease by electroporation versus gene gun generates potent and similar immune responses.电穿孔与基因枪传递阿尔茨海默病 DNA 疫苗产生强大且相似的免疫反应。
Neurodegener Dis. 2012;10(1-4):261-4. doi: 10.1159/000333359. Epub 2012 Feb 1.
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Gene vaccination to bias the immune response to amyloid-beta peptide as therapy for Alzheimer disease.基因疫苗接种以偏向对淀粉样β肽的免疫反应作为阿尔茨海默病的治疗方法。
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Short amyloid-beta (Abeta) immunogens reduce cerebral Abeta load and learning deficits in an Alzheimer's disease mouse model in the absence of an Abeta-specific cellular immune response.短淀粉样β蛋白（Aβ）免疫原在缺乏Aβ特异性细胞免疫反应的情况下，可降低阿尔茨海默病小鼠模型中的脑Aβ负荷和学习缺陷。
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The MultiTEP platform-based Alzheimer's disease epitope vaccine activates a broad repertoire of T helper cells in nonhuman primates.基于 MultiTEP 平台的阿尔茨海默病表位疫苗在非人灵长类动物中激活了广泛的辅助性 T 细胞库。
Alzheimers Dement. 2014 May;10(3):271-83. doi: 10.1016/j.jalz.2013.12.003. Epub 2014 Feb 20.
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Immunogenicity of DNA- and recombinant protein-based Alzheimer disease epitope vaccines.基于DNA和重组蛋白的阿尔茨海默病表位疫苗的免疫原性
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Assessment of multifunctional contrast agent probes in neuroimaging: Implications of nanopharmaceutical therapeutic interventions.神经成像中多功能造影剂探针的评估：纳米药物治疗干预的意义。
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Alzheimers Dement. 2014 May;10(3):284-95. doi: 10.1016/j.jalz.2013.04.505. Epub 2013 Jul 31.

本文引用的文献

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The usefulness and challenges of transgenic mouse models in the study of Alzheimer's disease.转基因小鼠模型在阿尔茨海默病研究中的作用和挑战。
CNS Neurol Disord Drug Targets. 2010 Aug;9(4):386-94. doi: 10.2174/187152710791556168.
2
Electroporation for DNA immunization: clinical application.电穿孔法用于 DNA 免疫接种：临床应用。
Expert Rev Vaccines. 2010 May;9(5):503-17. doi: 10.1586/erv.10.42.
3
Inflammation, immunity, and Alzheimer's disease.炎症、免疫与阿尔茨海默病。
CNS Neurol Disord Drug Targets. 2010 Apr;9(2):129-31. doi: 10.2174/187152710791012008.
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Can Alzheimer disease be prevented by amyloid-beta immunotherapy?阿尔茨海默病能否通过淀粉样蛋白-β免疫疗法预防？
Nat Rev Neurol. 2010 Feb;6(2):108-19. doi: 10.1038/nrneurol.2009.219.
5
Comparative performance of a licensed anthrax vaccine versus electroporation based delivery of a PA encoding DNA vaccine in rhesus macaques.许可的炭疽疫苗与基于电穿孔的 PA 编码 DNA 疫苗在恒河猴中的比较性能。
Vaccine. 2010 Jan 22;28(4):1056-61. doi: 10.1016/j.vaccine.2009.10.111. Epub 2009 Nov 5.
6
DNA prime-protein boost increased the titer, avidity and persistence of anti-Abeta antibodies in wild-type mice.DNA 初免-蛋白加强免疫提高了野生型小鼠抗 Abeta 抗体的滴度、亲合力和持久性。
Gene Ther. 2010 Feb;17(2):261-71. doi: 10.1038/gt.2009.140. Epub 2009 Oct 29.
7
Administration of HPV DNA vaccine via electroporation elicits the strongest CD8+ T cell immune responses compared to intramuscular injection and intradermal gene gun delivery.与肌肉注射和皮内基因枪递送相比，通过电穿孔接种人乳头瘤病毒（HPV）DNA疫苗可引发最强的CD8 + T细胞免疫反应。
Vaccine. 2009 Sep 4;27(40):5450-9. doi: 10.1016/j.vaccine.2009.07.005. Epub 2009 Jul 19.
8
DNA vaccination protects against an influenza challenge in a double-blind randomised placebo-controlled phase 1b clinical trial.在一项双盲随机安慰剂对照1b期临床试验中，DNA疫苗接种可预防流感攻击。
Vaccine. 2009 Apr 21;27(18):2506-12. doi: 10.1016/j.vaccine.2009.02.061. Epub 2009 Feb 24.
9
Active and passive Abeta-immunotherapy: preclinical and clinical studies and future directions: part I.主动和被动β-淀粉样蛋白免疫疗法：临床前和临床研究及未来方向：第一部分
CNS Neurol Disord Drug Targets. 2009 Mar;8(1):1-6. doi: 10.2174/187152709787601849.
10
Potentiation of an anthrax DNA vaccine with electroporation.通过电穿孔增强炭疽DNA疫苗效果
Vaccine. 2008 Sep 19;26(40):5216-22. doi: 10.1016/j.vaccine.2008.03.064. Epub 2008 Apr 16.

电穿孔与基因枪传递阿尔茨海默病 DNA 疫苗产生强大且相似的免疫反应。

Delivery of a DNA vaccine for Alzheimer's disease by electroporation versus gene gun generates potent and similar immune responses.

机构信息

Department of Molecular Immunology, Institute for Molecular Medicine, Huntington Beach, Calif 92647, USA.

出版信息

Neurodegener Dis. 2012;10(1-4):261-4. doi: 10.1159/000333359. Epub 2012 Feb 1.

DOI:10.1159/000333359
PMID:22301697
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3363347/
Abstract

BACKGROUND

Induction of a humoral response against amyloid-β peptide may be beneficial for Alzheimer's disease (AD) patients and may alleviate the onset and progression of AD. DNA-based vaccination provides a unique alternative method of immunization for treatment and prevention of AD. Currently, the two major delivery methods used for enhancing DNA uptake and immune responses to DNA vaccines in humans are electroporation (EP) and gene gun (GG).

OBJECTIVE

The goal of this translational study was to evaluate the efficacy of an AD DNA epitope vaccine (DepVac) delivered intramuscularly by EP or intradermally by GG.

METHODS

Humoral and cellular immune responses to immunization with DepVac were evaluated by ELISA and ELISPOT, respectively. Functional activity of the antibodies was also assessed.

RESULTS

EP- and GG-mediated immunizations with DepVac induced similar anti-amyloid-β (Aβ) antibody and T cell responses. Anti-Aβ antibodies bound to amyloid plaques in AD brain tissue and to toxic forms of Aβ(42) peptide.

CONCLUSION

Both delivery methods are effective at promoting potent antibodies specific for Aβ.

摘要

背景

诱导针对淀粉样蛋白-β肽的体液反应可能对阿尔茨海默病（AD）患者有益，并可能减轻 AD 的发病和进展。基于 DNA 的疫苗接种为 AD 的治疗和预防提供了一种独特的免疫接种替代方法。目前，用于增强人类对 DNA 疫苗的 DNA 摄取和免疫反应的两种主要递送方法是电穿孔（EP）和基因枪（GG）。

目的

本转化研究的目的是评估 AD DNA 表位疫苗（DepVac）通过 EP 肌肉内给药或 GG 皮内给药的疗效。

方法

通过 ELISA 和 ELISPOT 分别评估免疫接种 DepVac 后的体液和细胞免疫反应。还评估了抗体的功能活性。

结果

EP 和 GG 介导的 DepVac 免疫诱导了相似的抗淀粉样蛋白-β（Aβ）抗体和 T 细胞反应。抗 Aβ 抗体与 AD 脑组织中的淀粉样斑块以及有毒形式的 Aβ（42）肽结合。

结论

两种递送方法都能有效地促进针对 Aβ 的强效抗体。