Vaccine efficacy of transcutaneous immunization with amyloid β using a dissolving microneedle array in a mouse model of Alzheimer's disease
Vaccine efficacy of transcutaneous immunization with amyloid β using a dissolving microneedle array in a mouse model of Alzheimer's disease
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DOI：
10.1016/j.jneuroim.2013.11.002
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发表时间：
2014-01-15
影响因子：
3.3
通讯作者：
Nakagawa, Shinsaku
中科院分区：
文献类型：
--
作者：
Matsuo, Kazuhiko;Okamoto, Hideaki;Nakagawa, Shinsaku
基于淀粉样蛋白级联假说的阿尔茨海默病（AD）疫苗治疗最近引起了人们对治疗阿尔茨海默病的关注。使用包含1-42个氨基酸残基（Aβ1-42）的淀粉样蛋白r3肽（Aβ）作为抗原的注射免疫在小鼠中显示出治疗效果；然而，这种注射型Aβ1-42疫苗的临床试验因浸润大脑的Th1细胞过度激活而引发脑膜脑炎的严重不良反应而停止。由于最近的研究表明，经皮免疫（TCI）很可能引发以Th2为主的免疫反应，因此TCI有望有效治疗AD，且不会引起不良反应。此前报道的 TCI 程序采用了复杂且不切实际的疫苗接种程序；因此，需要建立一种简单、易用、新颖的 TCI 方法。在这项研究中，我们使用我们的新型可溶性微针阵列（MicroHyala；MH）研究了含有 A beta 1-42 的 TCI 对抗 AD 的疫苗功效。通过简单且低侵入性地将含有 A beta 1-42 的 MH 应用于皮肤，基于 MH 的 TCI 诱导抗 A beta 1-42 免疫反应。不幸的是，这种 TCI 系统对认知功能和 Th2 主导的免疫反应几乎没有显着改善，这表明需要进一步修改。 (c) 2013 Elsevier B.V. 保留所有权利。
Vaccine therapy for Alzheimer's disease (AD) based on the amyloid cascade hypothesis has recently attracted attention for treating AD. Injectable immunization using amyloid r3 peptide (A beta) comprising 1-42 amino-acid residues (A beta 1-42) as antigens showed therapeutic efficacy in mice; however, the clinical trial of this injected A beta 1-42 vaccine 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, TCI is expected to be effective in treating AD without inducing adverse reactions. Previously reported TCI procedures employed complicated and impractical vaccination procedures; therefore, a simple, easy-to-use, and novel TCI approach needs to be established. In this study, we investigated the vaccine efficacy of an A beta 1-42-containing TCI using our novel dissolving microneedle array (MicroHyala; MH) against AD. MH-based TCI induced anti-A beta 1-42 immune responses by simple and low-invasive application of A beta 1-42-containing MH to the skin. Unfortunately, this TCI system resulted in little significant improvement in cognitive function and Th2-dominant immune responses, suggesting the need for further modification. (c) 2013 Elsevier B.V. All rights reserved.