title: Comparison of Efficacy of Preventive and Therapeutic Vaccines Targeting the N Terminus of β-Amyloid in an Animal Model of Alzheimer's Disease.
abstract: Previously, we reported that Alzheimer's disease (AD) epitope vaccines (EVs) composed of N-terminal β-amyloid (Aβ42) B cell epitope fused with universal foreign T helper (Th) epitope(s) were immunogenic, potent, and safe in different amyloid precursor protein (APP) transgenic mice with early AD-like pathology. However, developing an effective therapeutic vaccine is much more challenging, especially when a self-antigen such as Aβ42is a target. Here, we directly compare the efficacy of anti-Aβ42antibodies in Tg2576 mice with low or high levels of AD-like pathology at the start of immunizations: 6-6.5 months for preventive vaccinations and 16-19 months for therapeutic vaccinations. EV in a preventive setting induced high levels of anti-Aβ antibodies, significantly reducing pathologic forms of Aβ in the brains of Tg2576 mice. When used therapeutically for immunesenescent Tg2576 mice, EV induced low levels of antibodies not sufficient for clearing of AD-like pathology. Separately, we demonstrated that EV was also not effective in 11-11.5-month-old Tg2576 mice with moderate AD-like pathology. However, we augmented the titers of anti-Aβ antibodies in transgenic (Tg) mice of the same age possessing the pre-existing memory Th cells and detected a significant decrease in diffuse and core plaques in cortical regions compared to control animals along with improved novel object recognition performance.
authors.affiliation: Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA 92697, USA.
authors.forename: Irina
authors.initials: I
authors.lastname: Petrushina
authors.affiliation: Department of Molecular Immunology, Institute for Molecular Medicine, Huntington Beach, CA 92647, USA.
authors.forename: Hayk
authors.initials: H
authors.lastname: Davtyan
authors.affiliation: Department of Molecular Immunology, Institute for Molecular Medicine, Huntington Beach, CA 92647, USA.
authors.forename: Armine
authors.initials: A
authors.lastname: Hovakimyan
authors.affiliation: Department of Molecular Immunology, Institute for Molecular Medicine, Huntington Beach, CA 92647, 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 92697, USA.
authors.forename: Giselle F
authors.initials: GF
authors.lastname: Passos
authors.affiliation: Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA 92697, USA.
authors.forename: David H
authors.initials: DH
authors.lastname: Cribbs
authors.affiliation: Department of Molecular Immunology, Institute for Molecular Medicine, Huntington Beach, CA 92647, USA. Electronic address: aghochikyan@immed.org.
authors.forename: Anahit
authors.initials: A
authors.lastname: Ghochikyan
authors.affiliation: Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA 92697, USA; Department of Molecular Immunology, Institute for Molecular Medicine, Huntington Beach, CA 92647, USA. Electronic address: magadjanyan@immed.org.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Agadjanyan
mesh_terms: D000544:Alzheimer Disease / Q000276:immunology* / Q000517:prevention & control / Q000628:therapy; D016229:Amyloid beta-Peptides / Q000276:immunology*; D000818:Animals; D000906:Antibodies / Q000276:immunology; D001253:Astrocytes / Q000276:immunology / Q000378:metabolism; D001921:Brain / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D000939:Epitopes / Q000276:immunology; D007114:Immunization; D051379:Mice; D008822:Mice, Transgenic; D009457:Neuroglia / Q000276:immunology / Q000378:metabolism; D010446:Peptide Fragments / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000378:metabolism; D014612:Vaccines / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D016229:Amyloid beta-Peptides; D000906:Antibodies; D000939:Epitopes; D010446:Peptide Fragments; D014612:Vaccines
keywords: Alzheimer’s disease; Aβ-pathology; amyloid-β; epitope vaccine; immune responses; inflammation; microhemorrhages; novel object recognition; preventive and therapeutic vaccines