title: Epitope-based DNA vaccine for Alzheimer's disease: translational study in macaques.
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.
authors.affiliation: Ichor Medical Systems, San Diego, CA, USA.
authors.forename: Claire F
authors.initials: CF
authors.lastname: Evans
authors.affiliation: 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.
authors.forename: Hayk
authors.initials: H
authors.lastname: Davtyan
authors.affiliation: Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA, USA.
authors.forename: Irina
authors.initials: I
authors.lastname: Petrushina
authors.affiliation: Department of Molecular Immunology, Institute for Molecular Medicine, Huntington Beach, CA, USA.
authors.forename: Armine
authors.initials: A
authors.lastname: Hovakimyan
authors.affiliation: Department of Molecular Immunology, Institute for Molecular Medicine, Huntington Beach, CA, USA.
authors.forename: Arpine
authors.initials: A
authors.lastname: Davtyan
authors.affiliation: Ichor Medical Systems, San Diego, CA, USA.
authors.forename: Drew
authors.initials: D
authors.lastname: Hannaman
authors.affiliation: Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA, USA; Department of Neurology, University of California, Irvine, Irvine, CA, USA.
authors.forename: David H
authors.initials: DH
authors.lastname: Cribbs
authors.affiliation: 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.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Agadjanyan
authors.affiliation: Department of Molecular Immunology, Institute for Molecular Medicine, Huntington Beach, CA, USA.
authors.forename: Anahit
authors.initials: A
authors.lastname: Ghochikyan
mesh_terms: D000544:Alzheimer Disease / Q000276:immunology* / Q000628:therapy*; D023582:Alzheimer Vaccines / Q000627:therapeutic use*; D016229:Amyloid beta-Peptides / Q000276:immunology; D000818:Animals; D000906:Antibodies / Q000097:blood / Q000276:immunology; D045744:Cell Line, Tumor; D004306:Dose-Response Relationship, Immunologic; D018984:Epitopes, T-Lymphocyte; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D008137:Longitudinal Studies; D008213:Lymphocyte Activation; D008253:Macaca mulatta; D008297:Male; D058225:Plaque, Amyloid / Q000276:immunology; D011897:Random Allocation; D006377:T-Lymphocytes, Helper-Inducer / Q000502:physiology*; D013997:Time Factors; D057170:Translational Research, Biomedical; D019444:Vaccines, DNA / Q000276:immunology / Q000627:therapeutic use
chemical_list: D023582:Alzheimer Vaccines; D016229:Amyloid beta-Peptides; D000906:Antibodies; D018984:Epitopes, T-Lymphocyte; D007074:Immunoglobulin G; D019444:Vaccines, DNA
keywords: Alzheimer's disease; Amyloid beta; Antibody response; Cellular immune response; DNA vaccine; Electroporation; Epitope vaccine; Rhesus macaques; Translational
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