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: Kazuhiko Matsuo, Hideaki Okamoto, Yasuaki Kawai, Ying-Shu Quan, Fumio Kamiyama, Sachiko Hirobe, Naoki Okada, Shinsaku Nakagawa
• Journal: Journal of neuroimmunology (J Neuroimmunol) Vol. 266 Issue 1-2 Pg. 1-11 (Jan 15 2014) ISSN: 1872-8421 [Electronic] Netherlands
• PMID: 24315156 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier B.V. All rights reserved.

Chemical References

• Amyloid beta-Peptides
• Amyloid beta-Protein Precursor
• Immunoglobulin G
• PSEN1 protein, human
• Peptide Fragments
• Presenilin-1
• amyloid beta-protein (1-40)
• amyloid beta-protein (1-42)

Topics

• Administration, Cutaneous
• Alzheimer Disease (blood, genetics, pathology, therapy)
• Amyloid beta-Peptides (blood, immunology)
• Amyloid beta-Protein Precursor (genetics)
• Animals
• Brain (metabolism)
• Disease Models, Animal
• Escape Reaction (physiology)
• Exploratory Behavior (physiology)
• Humans
• Immunoglobulin G (blood)
• Immunotherapy, Active (methods)
• Maze Learning (physiology)
• Mice
• Mice, Transgenic
• Mutation (genetics)
• Peptide Fragments (blood, immunology)
• Presenilin-1 (genetics)
• Reaction Time (physiology)
• Time Factors