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Evaluation of a DNA Aβ42 vaccine in adult rhesus monkeys (Macaca mulatta): antibody kinetics and immune profile after intradermal immunization with full-length DNA Aβ42 trimer


Year of Publication:
Contact PI Name:
Doris Lambracht-Washington
Contact PI Affiliation:
Department of Neurology and Neurotherapeutics, UT Southwestern Medical Center, Dallas, Texas, USA
Min Fu, Pat Frost, Roger N. Rosenberg
Primary Reference (PubMED ID):
Funding Source:
National Institute on Aging (NIA)
Zale Foundation
McCune Foundation
Alliance of Women for Alzheimer Research and Education (AWARE)
Presbyterian Village North
Freiberger, Losinger and Denker Family Funds
The Rudman Foundation
Study Goal and Principal Findings:

Aggregated amyloid-β peptide 1–42 (Aβ42), derived from the cellular amyloid precursor protein, is one of the pathological hallmarks of Alzheimer’s disease (AD). Although active immunization against Aβ42 peptide was successful in AD mouse models and led to removal of plaques and improved memory, a similar clinical trial in humans (Aβ42 peptide immunization with QS-21 adjuvant) was stopped in phase II, when 6% of the treated patients developed encephalitis. Currently ongoing passive immunizations with the injection of preformed monoclonal antibodies against different epitopes within the Aβ1–42 peptide, which do not lead to activation of the immune system, have shown some effects in slowing AD pathology. Active DNA Aβ42 immunizations administered with the gene gun into the skin are noninflammatory because they activate a different T-cell population (Th2) with different cytokine responses eliciting a different humoral immune response. We present our findings in rhesus macaques that underwent the DNA Aβ42 immunization via gene gun delivery into the skin. Six rhesus monkeys received two different doses of a DNA Aβ42 trimer vaccine. The humoral immune response was analyzed from blood throughout the study, and cellular immune responses were determined in peripheral blood mononuclear cells (PBMCs) after three and six immunizations. DNA Aβ42 trimer immunization led to high titer antibody responses in the nonhuman primate (NHP) model. Antibodies generated in the rhesus monkeys following DNA Aβ42 immunization detected amyloid plaques consisting of human Aβ42 peptide in the brain of the triple-transgenic AD mouse model. T-cell responses showed no interferon (IFN)-γ- and interleukin (IL)-17-producing cells from PBMCs in Enzyme-Linked ImmunoSpot assays after three immunization time points. At six immunization time points, IFN-γ- and IL-17-producing cells were found in immunized animals as well as in control animals and were thus considered nonspecific and not due to the immunization regimen. IFN-γ and IL-17 secretion in response to Aβ42 peptide restimulation became undetectable after a 3-month rest period. Intradermal DNA Aβ42 immunization delivered with the gene gun produces a high antibody response in NHPs and is highly likely to be effective and safe in a clinical AD prevention trial in patients.

Therapeutic Agent

Therapeutic Information:
Therapy Type:
Biologic - Immunotherapy(active)
Therapeutic Agent:
DNA Aβ42 Vaccine
Therapeutic Target:
beta Amyloid Peptide 42

Animal Model

Model Information:
Non Human Primate
Model Type:
Strain/Genetic Background:
Not Applicable

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
Plasma-Interferon (IFN) gamma
Interleukin 17 (IL-17)
Interleukin 4 (IL-4)
Brain-beta Amyloid Peptide 42
Brain-beta Amyloid Deposits
Cell Biology
Cell Proliferation
Antibody Titers
Antibody Isotypes
Antibody Target Specificity
T Cell Response
Target Engagement (Reduction beta Amyloid Peptides-Brain)
Blood/Serum Clinical Chemistry