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

Bibliographic

Year of Publication:
2014
Contact PI Name:
Nakagawa Shinsaku
Contact PI Affiliation:
Laboratory of Biotechnology and Therapeutics, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan
Co-Authors:
Kazuhiko Matsuo, Hideaki Okamoto, Yasuaki Kawai, Ying-Shu Quan, Fumio Kamiyama, Sachiko Hirobe, Naoki Okada
Primary Reference (PubMED ID):
Funding Source:
Japanese Ministry of Education, Culture, Sports, Science and Technology (MEXT)
Advanced Research for Medical Products Mining Program of Japan
Study Goal and Principal Findings:

Vaccine therapy for AD has recently attracted attention for treating this disorder. Injectable immunization using  Aβ1–42 as  an antigen 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. It has been suggested that transcutaneous immunization (TCI) is likely to elicit a Th2 dominant immune response and therefore avoid Th1 mediated inflammation. In this study, the investigators tested the efficacy of an Aβ1–42-containing TCI- vaccine using a novel dissolving micro needle array (MicroHyala; MH). And the Tg APPPS1 Mouse model of AD. MH-based TCI induced anti-Aβ1–42 immune responses by simple and low-invasive application of Aβ1–42-containing MH to the skin. The TCI system was found to have significant advantages because it is a simple, easy-to-use, painless, and minimally invasive vaccination method. This TCI system resulted in little significant improvement in cognitive function and in eliciting a Th2-dominant immune responses, suggesting the need for further modification.

Therapeutic Agent

Therapeutic Information:
Therapy Type:
Biologic - Immunotherapy(active)
Therapeutic Agent:
beta Amyloid Peptide 1-42
Therapeutic Target:
beta Amyloid Peptide

Animal Model

Model Information:
Species:
Mouse
Model Type:
APPxPS1
Strain/Genetic Background:
C57BL/6

Experimental Design

Is the following information reported in the study?:
Power/Sample Size Calculation
Randomized into Groups
Blinded for Treatment
Blinded for Outcome Measures
Pharmacokinetic Measures
Pharmacodynamic Measures
Toxicology Measures
ADME Measures
Biomarkers
Dose
Formulation
Route of Delivery
Duration of Treatment
Frequency of Administration
Age of Animal at the Beginning of Treatment
Age of Animal at the End of Treatment
Sex as a Biological Variable
Study Balanced for Sex as a Biological Variable
Number of Premature Deaths
Number of Excluded Animals
Statistical Plan
Genetic Background
Inclusion/Exclusion Criteria Included
Conflict of Interest

Outcomes

Outcome Measured
Outcome Parameters
Behavioral
Novel Object Recognition Test (NORT)
Morris Water Maze
Histopathology
beta Amyloid Load
Biochemical
Brain-beta Amyloid Peptide 40
Brain-beta Amyloid Peptide 42
Brain-beta Amyloid Oligomers
Serum-beta Amyloid Peptide 40
Serum-beta Amyloid Peptide 42
Immunology
Antibody Titers
T Cell Response
Antibody Isotypes