title: The MultiTEP platform-based Alzheimer's disease epitope vaccine activates a broad repertoire of T helper cells in nonhuman primates.
abstract: BACKGROUND
  As a prelude to clinical trials we have characterized B- and T-cell immune responses in macaques to AD vaccine candidates: AV-1955 and its slightly modified version, AV-1959 (with 3 additional promiscuous Th epitopes).
  
  
  METHODS
  T- and B-cell epitope mapping was performed using the ELISPOT assay and competition ELISA, respectively.
  
  
  RESULTS
  AV-1955 and AV-1959 did not stimulate potentially harmful autoreactive T cells, but instead activated a broad but individualized repertoire of Th cells specific to the MultiTEP platform in macaques. Although both vaccines induced robust anti-Aβ antibody responses without producing antibodies specific to Th epitopes of MultiTEP platforms, analyses of cellular immune responses in macaques demonstrated that the addition of Th epitopes in the case of AV-1959 created a more potent, superior vaccine.
  
  
  CONCLUSIONS
  AV-1959 is a promising vaccine candidate capable of producing therapeutically potent anti-amyloid antibody in a broader population of vaccinated subjects with high MHC class II gene polymorphisms.
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: Department of Molecular Immunology, Institute for Molecular Medicine, Huntington Beach, CA, USA.
authors.forename: Anahit
authors.initials: A
authors.lastname: Ghochikyan
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: 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
mesh_terms: D000544:Alzheimer Disease / Q000276:immunology* / Q000628:therapy*; D023582:Alzheimer Vaccines / Q000276:immunology* / Q000627:therapeutic use*; D016229:Amyloid beta-Peptides / Q000276:immunology; D000818:Animals; D000906:Antibodies / Q000276:immunology; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D058501:Enzyme-Linked Immunospot Assay; D018604:Epitope Mapping; D018985:Epitopes, B-Lymphocyte; D018984:Epitopes, T-Lymphocyte; D005260:Female; D008213:Lymphocyte Activation; D008253:Macaca mulatta; D008297:Male; D008810:Mice, Inbred C57BL; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D019444:Vaccines, DNA / Q000627:therapeutic use
chemical_list: D023582:Alzheimer Vaccines; D016229:Amyloid beta-Peptides; D000906:Antibodies; D018985:Epitopes, B-Lymphocyte; D018984:Epitopes, T-Lymphocyte; D019444:Vaccines, DNA
keywords: AD epitope vaccine; Alzheimer's disease (AD); Electroporation; Mapping of B- and T-cell immune responses; Rhesus macaques