title: Vaccine efficacy of transcutaneous immunization with amyloid β using a dissolving microneedle array in a mouse model of Alzheimer's disease.
abstract: Vaccine therapy for Alzheimer's disease (AD) based on the amyloid cascade hypothesis has recently attracted attention for treating AD. Injectable immunization using amyloid β peptide (Aβ) comprising 1-42 amino-acid residues (Aβ1-42) as antigens showed therapeutic efficacy in mice; however, the clinical trial of this injected Aβ1-42 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 Aβ1-42-containing TCI using our novel dissolving microneedle array (MicroHyala; MH) against AD. MH-based TCI induced anti-Aβ1-42 immune responses by simple and low-invasive application of Aβ1-42-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.
authors: Laboratory of Biotechnology and Therapeutics, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors: Kazuhiko
authors: K
authors: Matsuo
authors: Laboratory of Biotechnology and Therapeutics, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors: Hideaki
authors: H
authors: Okamoto
authors: Laboratory of Biotechnology and Therapeutics, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors: Yasuaki
authors: Y
authors: Kawai
authors: CosMED Pharmaceutical Co. Ltd., 32 Higashikujokawanishi-cho, Minami-ku, Kyoto 601-8014, Japan.
authors: Ying-Shu
authors: YS
authors: Quan
authors: CosMED Pharmaceutical Co. Ltd., 32 Higashikujokawanishi-cho, Minami-ku, Kyoto 601-8014, Japan.
authors: Fumio
authors: F
authors: Kamiyama
authors: Laboratory of Biotechnology and Therapeutics, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors: Sachiko
authors: S
authors: Hirobe
authors: Laboratory of Biotechnology and Therapeutics, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan. Electronic address: okada@phs.osaka-u.ac.jp.
authors: Naoki
authors: N
authors: Okada
authors: Laboratory of Biotechnology and Therapeutics, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan. Electronic address: nakagawa@phs.osaka-u.ac.jp.
authors: Shinsaku
authors: S
authors: Nakagawa
mesh_terms: D000279:Administration, Cutaneous; D000544:Alzheimer Disease / Q000097:blood / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D016229:Amyloid beta-Peptides / Q000097:blood / Q000276:immunology*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D001921:Brain / Q000378:metabolism; D004195:Disease Models, Animal; D004924:Escape Reaction / Q000502:physiology; D005106:Exploratory Behavior / Q000502:physiology; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D016233:Immunotherapy, Active / Q000379:methods*; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D010446:Peptide Fragments / Q000097:blood / Q000276:immunology*; D053764:Presenilin-1 / Q000235:genetics; D011930:Reaction Time / Q000502:physiology; D013997:Time Factors
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D007074:Immunoglobulin G; C508853:PSEN1 protein, human; D010446:Peptide Fragments; D053764:Presenilin-1; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42)
keywords: AD; ANOVA; Alzheimer's disease; Aβ; CC; CNS; CT; Dissolving microneedle array; EC; ELISA; HIPP; HRP; IDI; LC; Langerhans cell; MH; MWMT; MicroHyala; Morris water maze test; N.D.; NORT; TBS; TBS-T; TCI; TQ; Transcutaneous immunization; Tris–HCl-buffered saline; Tris–HCl-buffered saline containing 0.05% Tween-20; Vaccine therapy; amyloid β peptide; analysis of variance; central nervous system; cholera toxin; cingulate cortex; entorhinal cortex; enzyme-linked immunosorbent assay; hippocampus; horseradish peroxidase; intradermal immunization; not detectable; novel object recognition test; target quadrant; transcutaneous immunization