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

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• 作者：Kazuhiko Matsuo ; Hideaki Okamoto ; Yasuaki Kawai ; Ying-Shu Quan ; Fumio Kamiyama ; Sachiko Hirobe ; Naoki Okada ; Shinsaku Nakagawa
• 关键词：A尾 ; amyloid 尾 peptide ; AD ; Alzheimer's disease ; ANOVA ; analysis of variance ; CC ; cingulate cortex ; CNS ; central nervous system ; CT ; cholera toxin ; EC ; entorhinal cortex ; ELISA ; enzyme-linked immunosorbent assay ; HIPP ; hippocampus ; HRP ; horseradish peroxidase ; IDI ; intradermal immunization ; LC ; Langerhans cell ; MH ; MicroHyala ; MWMT ; Morris water maze test ; N.D. ; not detectable ; NORT ; novel object recognition test ; TBS ; Tris&ndash ; HCl-buffered saline ; TBS-T ; Tris&ndash ; HCl-buffered saline contai
• 刊名：Journal of Neuroimmunology
• 出版年：15 January, 2014
• 年：2014
• 卷：266
• 期：1-2
• 页码：1-11
• 全文大小：1689 K

文摘

Vaccine therapy for Alzheimer's disease (AD) based on the amyloid cascade hypothesis has recently attracted attention for treating AD. Injectable immunization using amyloid 尾 peptide (A尾) comprising 1-42 amino-acid residues (A尾1-42) as antigens showed therapeutic efficacy in mice; however, the clinical trial of this injected A尾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尾1-42-containing TCI using our novel dissolving microneedle array (MicroHyala; MH) against AD. MH-based TCI induced anti-A尾1-42 immune responses by simple and low-invasive application of A尾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.