Claire F Evans1, Hayk Davtyan2, Irina Petrushina3, Armine Hovakimyan4, Arpine Davtyan4, Drew Hannaman1, David H Cribbs5, Michael G Agadjanyan6, Anahit Ghochikyan4. 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.
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.
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