Development of transcutaneous immunization system for Alzheimer's disease

阿尔茨海默病经皮免疫系统的开发

• 批准号: 24790154
• 负责人: MATSUO Kazuhiko
• 金额: $ 2.91万
• 依托单位: Kinki University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2012
• 资助国家: 日本
• 起止时间: 2012-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-24790154/
• 关键词: アルツハイマー型認知症; 経皮ワクチン; 自己溶解型マイクロニードル; アルツハイマー病

Vaccine therapy for Alzheimer's disease (AD) based on the amyloid cascade hypothesis has recently attracted attention for treatment of AD. Injectable immunization of amyloid beta peptide (Ab) as antigens showed therapeutic efficacy; therefore, a clinical trial was conducted. However, the clinical trial was stopped due to the incidence of meningoencephalitis caused by excess activation of Th1 cells infiltrating the brain as a serious adverse reaction. Because recent studies have suggested that transcutaneous immunization (TCI) is likely to elicit Th2-dominant immune responses, in this study, we investigated the vaccine efficacy of TCI against AD using a novel dissolving microneedle array (MicroHyala; MH). Our TCI induced anti-Ab1-42 immune responses by simple and low-invasive application of Ab-containing MH to the skin. Unfortunately, this TCI resulted in little significant improvement in cognitive function and Th2-dominant immune responses, suggesting the need for further modification.

基于淀粉样蛋白级联假说的阿尔茨海默病（AD）疫苗疗法最近引起了人们对AD治疗的关注。淀粉样蛋白β肽（Ab）作为抗原的注射免疫显示出治疗效果;因此，进行了临床试验。然而，由于Th 1细胞过度激活浸润大脑导致脑膜脑炎的发生是严重的不良反应，临床试验被停止。由于最近的研究表明，经皮免疫（TCI）可能会引起Th 2-显性免疫应答，在这项研究中，我们研究了疫苗的效力TCI对AD使用一种新的溶解微针阵列（MicroHyala; MH）。我们的TCI诱导抗Ab 1 -42的免疫反应，通过简单和低侵入性的应用程序的Ab含有MH的皮肤。不幸的是，这种TCI导致认知功能和Th 2-显性免疫应答几乎没有显著改善，这表明需要进一步修改。

项目成果

Vaccine efficacy of transcutaneous immunization with amyloid β using a dissolving microneedle array in a mouse model of Alzheimer's disease

• DOI: 10.1016/j.jneuroim.2013.11.002
• 发表时间: 2014-01-15
• 期刊: JOURNAL OF NEUROIMMUNOLOGY
• 影响因子: 3.3
• 作者: Matsuo, Kazuhiko;Okamoto, Hideaki;Nakagawa, Shinsaku
• 通讯作者: Nakagawa, Shinsaku

Transcutaneous immunization using a dissolving microneedle array protects against tetanus, diphtheria, malaria, and influenza

• DOI: 10.1016/j.jconrel.2012.04.001
• 发表时间: 2012-06-28
• 期刊: JOURNAL OF CONTROLLED RELEASE
• 影响因子: 10.8
• 作者: Matsuo, Kazuhiko;Hirobe, Sachiko;Nakagawa, Shinsaku
• 通讯作者: Nakagawa, Shinsaku