Epitope-based DNA vaccine for Alzheimer's disease: Translational study in macaques |
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| Affiliation: | 1. Ichor Medical Systems, San Diego, CA, USA;2. Department of Molecular Immunology, Institute for Molecular Medicine, Huntington Beach, CA, USA;3. Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA, USA;4. Department of Neurology, University of California, Irvine, Irvine, CA, USA;1. Department of Psychology, National Taiwan University, Taipei, Taiwan;2. Department of Psychiatry, University of California at San Diego, San Diego, CA, USA;3. Department of Radiology, University of California at San Diego, San Diego, CA, USA;4. Department of Neurosciences, University of California at San Diego, San Diego, CA, USA;5. Veterans Affairs Boston Healthcare System, Boston, MA, USA;6. Department of Psychiatry, Boston University School of Medicine, Boston, MA, USA;7. Veterans Affairs San Diego Healthcare System, San Diego, CA, USA;1. Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, SC, USA;2. Department of Pediatrics, Medical University of South Carolina, Charleston, SC, USA;3. Department of Pathology and Laboratory Medicine Service, Ralph H. Johnson Veterans Administration Medical Center, Charleston, SC, USA;1. Office of Planning, Analysis & Evaluation, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA;2. Alzheimer''s Association, Chicago, IL, USA;3. Division of Neuroscience, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA;1. School of Materials Science, Japan Advanced Institute of Science and Technology (JAIST), 1-1 Asahidai, Nomi, Ishikawa 923-1292, Japan;2. Hanoi National University of Education, 136 Xuanthuy, Caugiay, Hanoi, Viet Nam;1. Department of Neurology, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland;2. Aging Research Center, Karolinska Institutet, Stockholm, Sweden;3. Karolinska Institutet Alzheimer Disease Research Center, Stockholm, Sweden;4. Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland;5. Department of Neurology, Kuopio University Hospital, Kuopio, Finland;6. Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland;7. Hospital District of North Karelia, Joensuu, Finland |
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| Abstract: | BackgroundClinical 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.MethodsHumoral 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.ResultsAV-1955 generates long-term, potent anti-Aβ antibodies and cellular immune responses specific to foreign T-helper epitopes but not to self-Aβ.ConclusionsThis translational study demonstrates that a DNA-based epitope vaccine for AD could be appropriate for human clinical testing. |
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