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Alzheimers Dement. 2014 May;10(3):284-95. doi: 10.1016/j.jalz.2013.04.505. Epub 2013 Jul 31.

Epitope-based DNA vaccine for Alzheimer's disease: translational study in macaques.

Author information

1
Ichor Medical Systems, San Diego, CA, USA.
2
Department of Molecular Immunology, Institute for Molecular Medicine, Huntington Beach, CA, USA; Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA, USA.
3
Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA, USA.
4
Department of Molecular Immunology, Institute for Molecular Medicine, Huntington Beach, CA, USA.
5
Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA, USA; Department of Neurology, University of California, Irvine, Irvine, CA, USA.
6
Department of Molecular Immunology, Institute for Molecular Medicine, Huntington Beach, CA, USA; Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA, USA. Electronic address: magadjanyan@immed.org.

Abstract

BACKGROUND:

Clinical trials with passive and active Alzheimer's disease (AD) vaccines suggest that early interventions are needed for improvement of cognitive and/or functional performance in patients, providing impetus for the development of safe and immunologically potent active vaccines targeting amyloid β (Aβ). The AN-1792 trial has indicated that Aβ-specific T cells may be unsafe for humans; therefore, other vaccines based on small Aβ epitopes are undergoing preclinical and clinical testing.

METHODS:

Humoral and cellular immune responses elicited in response to a novel DNA epitope-based vaccine (AV-1955) delivered to rhesus macaques using the TriGrid electroporation device were evaluated. Functional activities of anti-Aβ antibodies generated in response to vaccination were assessed in vitro.

RESULTS:

AV-1955 generates long-term, potent anti-Aβ antibodies and cellular immune responses specific to foreign T-helper epitopes but not to self-Aβ.

CONCLUSIONS:

This translational study demonstrates that a DNA-based epitope vaccine for AD could be appropriate for human clinical testing.

KEYWORDS:

Alzheimer's disease; Amyloid beta; Antibody response; Cellular immune response; DNA vaccine; Electroporation; Epitope vaccine; Rhesus macaques; Translational

PMID:
23916838
PMCID:
PMC3825833
DOI:
10.1016/j.jalz.2013.04.505
[Indexed for MEDLINE]
Free PMC Article
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