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J Neuroimmunol. 2014 Jan 15;266(1-2):1-11. doi: 10.1016/j.jneuroim.2013.11.002. Epub 2013 Nov 11.

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

Author information

1
Laboratory of Biotechnology and Therapeutics, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.
2
CosMED Pharmaceutical Co. Ltd., 32 Higashikujokawanishi-cho, Minami-ku, Kyoto 601-8014, Japan.
3
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.
4
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.

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.

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

PMID:
24315156
DOI:
10.1016/j.jneuroim.2013.11.002
[Indexed for MEDLINE]
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