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Immunogenicity, efficacy, safety, and mechanism of action of epitope vaccine (Lu AF20513) for Alzheimer's disease: prelude to a clinical trial


Year of Publication:
Contact PI Name:
Michael G. Agadjanyan
Contact PI Affiliation:
The Institute for Molecular Medicine, Huntington Beach, California, USA
Hayk Davtyan, Anahit Ghochikyan, Irina Petrushina, Armine Hovakimyan, Arpine Davtyan, Anna Poghosyan, Annette M. Marleau, Nina Movsesyan, Anatoly Kiyatkin, Suhail Rasool, et al.,
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:

The Alzheimer's disease (AD) process is understood to involve the accumulation of amyloid plaques and tau tangles in the brain. However, attempts at targeting the main culprits, neurotoxic Aβ peptides, have thus far proven unsuccessful for improving cognitive function. Recent clinical trials with passively administrated anti-Aβ antibodies failed to slow cognitive decline in mild to moderate AD patients, but suggest that an immunotherapeutic approach could be effective in patients with mild AD. Using an AD mouse model (Tg2576), we tested the immunogenicity (cellular and humoral immune responses) and efficacy (AD-like pathology) of clinical grade Lu AF20513 vaccine. We found that Lu AF20513 induces robust "non-self" T-cell responses and the production of anti-Aβ antibodies that reduce AD-like pathology in the brains of Tg2576 mice without inducing microglial activation and enhancing astrocytosis or cerebral amyloid angiopathy. A single immunization with Lu AF20513 induced strong humoral immunity in mice with preexisting memory T-helper cells. In addition, Lu AF20513 induced strong humoral responses in guinea pigs and monkeys. These data support the translation of Lu AF20513 to the clinical setting with the aims of: (1) inducing therapeutically potent anti-Aβ antibody responses in patients with mild AD, particularly if they have memory T-helper cells generated after immunizations with conventional tetanus toxoid vaccine, and (2) preventing pathological autoreactive T-cell responses.

Bibliographic Notes:
Full Author List: Hayk Davtyan, Anahit Ghochikyan, Irina Petrushina, Armine Hovakimyan, Arpine Davtyan, Anna Poghosyan, Annette M. Marleau, Nina Movsesyan, Anatoly Kiyatkin, Suhail Rasool, Anna Kirstine Larsen, Peter Juul Madsen, Karen Malene Wegener, Dorte Kornerup Ditlevsen, David H. Cribbs, Lars Ostergaard Pedersen, Michael G. Agadjanyan.

Michael G. Agadjanyan (The Institute for Molecular Medicine, Huntington Beach, California, USA)and Lars Ostergaard Pederson (H. Lundbeck A/S, Biologic, Copenhagen, Denmark) are corresponding authors on this paper.

Therapeutic Agent

Therapeutic Information:
Therapy Type:
Biologic - Immunotherapy(active)
Therapeutic Agent:
Lu AF20513 (DNA Epitope Vaccine)
Therapeutic Target:
beta Amyloid Peptide

Animal Model

Model Information:
Model Type:
Strain/Genetic Background:
Not Reported
Guinea Pig
Model Type:
Strain/Genetic Background:
Not Applicable
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
beta Amyloid Load
Vascular beta Amyloid Deposits
Activated Microglia
Activated Astrocytes
Brain-beta Amyloid Peptide 40
Brain-beta Amyloid Peptide 42
Interleukin 4 (IL-4) Production
Binding-beta Amyloid Fibrils
Binding-beta Amyloid Oligomers
Anti-beta Amyloid Antibody Titers
Anti-beta Amyloid Antibody Isotypes
T Cells
Interferon (IFN) gamma Production
T Cell Response