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Abeta42 gene vaccination reduces brain amyloid plaque burden in transgenic mice


Year of Publication:
Contact PI Name:
Roger N. Rosenberg
Contact PI Affiliation:
Alzheimer’s Diseases Center, Department of Neurology, University of Texas Southwestern Medical Center, Dallas, Texas, USA
Baoxi Qu, Philip J. Boyer, Stephen Albert Johnston, Linda S. Hynan
Primary Reference (PubMED ID):
Funding Source:
National Institute on Aging (NIA)
The Rudman Foundation
The Luttrell Foundation
Center for Biomedical Inventions at Arizona State University
The Winspear Family Special Center for Research on the Neuropathology of Alzheimer Disease
Study Goal and Principal Findings:

To demonstrate that in APPswe/PS1DeltaE9 transgenic mice, gene gun mediated Abeta42 gene vaccination elicits a high titer of anti-Abeta42 antibodies causal of a significant reduction of Abeta42 deposition in brain.Gene gun immunization is conducted with transgenic mice using the Abeta42 gene in a bacterial plasmid with the pSP72-E3L-Abeta42 construct. Enzyme-linked immunoabsorbent assays (ELISA) and Western blots are used to monitor anti-Abeta42 antibody levels in serum and Abeta42 levels in brain tissues. Enzyme-linked immunospot (ELISPOT) assays are used for detection of peripheral blood T cells to release gamma-interferon. Immunofluorescence detection of Abeta42 plaques and quantification of amyloid burden of brain tissue were measured and sections were analyzed with Image J (NIH) software.Gene gun vaccination with the Abeta42 gene resulted in high titers of anti-Abeta42 antibody production of the Th2-type. Levels of Abeta42 in treated transgenic mouse brain were reduced by 60-77.5%. The Mann-Whitney U-test P=0.0286.Was developed a gene gun mediated Abeta42 gene vaccination method that is efficient to break host Abeta42 tolerance without using adjuvant and induces a Th2 immune response. Abeta42 gene vaccination significantly reduces the Abeta42 burden of the brain in treated APPswe/PS1DeltaE9 transgenic mice with no overlap between treated and control mice.

Therapeutic Agent

Therapeutic Information:
Therapy Type:
Biologic - Immunotherapy(active)
Therapeutic Agent:
Abeta42 Gene Vaccine
Therapeutic Target:
beta Amyloid Peptide

Animal Model

Model Information:
Model Type:
Strain/Genetic Background:
Model Type:
Strain/Genetic Background:
Not Reported

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
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


Outcome Measured
Outcome Parameters
beta Amyloid Deposits
beta Amyloid Load
Brain-beta Amyloid Peptide 42
Plasma-beta Amyloid Peptide 42
Interferon (IFN) gamma
Plasma-beta Amyloid Peptides
T Cells
Anti-beta Amyloid Antibody Titers
Antibody Target Specificity
Anti-beta Amyloid Antibody Isotypes
Target Engagement (Reduction beta Amyloid Peptides-Brain)