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Low concentrations of anti-Abeta antibodies generated in Tg2576 mice by DNA epitope vaccine fused with 3C3d molecular adjuvant do not affect AD pathology


Year of Publication:
Contact PI Name:
David H. Cribbs
Contact PI Affiliation:
University of California, Irvine, Institute for Memory Impairments and Neurological Disorders, Irvine, California, USA
Nina Movsesyan, Hayk Davtyan, Mikayel Mkrtichyan, Irina Petrushina, Tigran Tiraturyan, Michael G. Agadjanyan, Anahit Ghochikyan
Primary Reference (PubMED ID):
Funding Source:
Alzheimer's Association
National Institute on Aging (NIA)
National Institute of Neurological Disorders and Stroke (NINDS)
Study Goal and Principal Findings:

To avoid problems associated with active immunization (e.g., AN-1792) of elderly AD patients, the authors have developed an active vaccination strategy using peptide- or DNA-based epitope vaccines. Here, the authors tested the efficacy of the DNA epitope vaccine p3Abeta 1–11-PADRE and the same vaccine fused with a component of complement 3C3d (p3Abeta 1–11-PADRE-3C3d) in a transgenic (Tg) mouse model of AD (Tg2576), of the H2bxs immune haplotype. The overall responses to both vaccines were very weak in Tg2576 mice despite the fact that the 3C3d molecular adjuvant significantly enhanced the anti-Abeta response to 3Abeta 1–11-PADRE. Importantly, generation of low antibody responses was associated with the strain of amyloid precursor protein Tg mice rather than with a molecular adjuvant, as a p3Abeta 1–11-PADRE-3C3d vaccine induced significantly higher antibody production in another AD mouse model- 3xTg-AD of the H2b haplotype. This study demonstrated that low concentrations of antibodies generated by both DNA vaccines were not sufficient for the reduction of Abeta pathology in the brains of vaccinated Tg2576 animals, confirming previous reports from preclinical studies and the AN-1792 clinical trials. These studies concluded that the concentration of anti-Abeta antibodies may be essential for the reduction of AD pathology. 

Therapeutic Agent

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

Animal Model

Model Information:
Model Type:
Strain/Genetic Background:
B6/SJL F1 background, H2bxs haplotype

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
Experiment Notes

Dosage, formulation and other details regarding immunization of mice are given in: Ghochikyan, A., Vasilevko, V., Petrushina, I., Tran, M., Sadzikava, N., Babikyan, D., Movsesyan, N., Tian, W., Ross, T.M., Cribbs, D.H., and Agadjanyan, M.G. (2003). Generation and characterization of the humoral immune response to DNA immunization with a chimeric b-amyloid-interleukin-4 minigene. Eur. J. Immunol. 33, 3232–3241 and Movsesyan, N., Ghochikyan, A., Mkrtichyan, M., Petrushina, I., Davtyan, H., Olkhanud, P.B., Head, E., Biragyn, A., Cribbs, D.H., and Agadjanyan, M.G. (2008a). Reducing AD-like pathology in 3xTg-AD mouse model by DNA epitope vaccine— a novel immunotherapeutic strategy. PLoS One 3, e21–e24.


Outcome Measured
Outcome Parameters
beta Amyloid Load
Brain-beta Amyloid Peptide 40
Brain-beta Amyloid Peptide 42
Antibody Titers
Humoral Response
Antibody Isotypes