title: Immunogenicity of epitope vaccines targeting different B cell antigenic determinants of human α-synuclein: feasibility study.
abstract: Immunotherapeutic approaches reducing α-synuclein deposits may provide therapeutic benefit for Dementia with Lewy Bodies (DLB). Immunization with full-length human α-synuclein (hα-Syn) protein in a Parkinson's disease mouse model decreased the accumulation of the aggregated forms of this protein in neurons and reduced neurodegeneration. To enhance the immunogenicity of candidate vaccines and to avoid the risk of autoreactive anti-hα-Syn T-helper (Th) cell responses, we generated three peptide-based epitope vaccines composed of different B-cell epitopes of hα-Syn fused with a "non-self" Th epitope from tetanus toxin (P30). Immunization of mice with these epitope vaccines produced high titers of anti-hα-Syn antibodies that bound to Lewy bodies (LBs) and Lewy neurites (LNs) in brain tissue from DLB cases and induced robust Th cell responses to P30, but not to hα-Syn. Further development of these first generation epitope vaccines may facilitate induction of anti-hα-Syn immunotherapy without producing potentially harmful autoreactive Th cell responses.
authors.affiliation: The Institute for Molecular Medicine, Department of Immunology, Huntington Beach, CA 92647, United States. Electronic address: aghochikyan@immed.org.
authors.forename: Anahit
authors.initials: A
authors.lastname: Ghochikyan
authors.affiliation: The Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA 92697, United States.
authors.forename: Irina
authors.initials: I
authors.lastname: Petrushina
authors.affiliation: The Institute for Molecular Medicine, Department of Immunology, Huntington Beach, CA 92647, United States; The Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA 92697, United States.
authors.forename: Hayk
authors.initials: H
authors.lastname: Davtyan
authors.affiliation: The Institute for Molecular Medicine, Department of Immunology, Huntington Beach, CA 92647, United States.
authors.forename: Armine
authors.initials: A
authors.lastname: Hovakimyan
authors.affiliation: The Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA 92697, United States.
authors.forename: Tommy
authors.initials: T
authors.lastname: Saing
authors.affiliation: The Institute for Molecular Medicine, Department of Immunology, Huntington Beach, CA 92647, United States.
authors.forename: Arpine
authors.initials: A
authors.lastname: Davtyan
authors.affiliation: The Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA 92697, United States; Department of Neurology, University of California, Irvine, CA 92697, United States.
authors.forename: David H
authors.initials: DH
authors.lastname: Cribbs
authors.affiliation: The Institute for Molecular Medicine, Department of Immunology, Huntington Beach, CA 92647, United States; The Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA 92697, United States. Electronic address: magadjanyan@immed.org.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Agadjanyan
mesh_terms: D000818:Animals; D000917:Antibody Formation; D001921:Brain / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018985:Epitopes, B-Lymphocyte / Q000235:genetics / Q000276:immunology*; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D016631:Lewy Bodies / Q000276:immunology / Q000378:metabolism; D020961:Lewy Body Disease / Q000276:immunology / Q000473:pathology; D051379:Mice; D016501:Neurites / Q000276:immunology / Q000378:metabolism; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology; D013744:Tetanus Toxin / Q000235:genetics; D014611:Vaccination; D014612:Vaccines / Q000235:genetics / Q000276:immunology*; D051844:alpha-Synuclein / Q000235:genetics / Q000276:immunology*
chemical_list: D018985:Epitopes, B-Lymphocyte; C091828:P30 tetanus toxin peptide; D010446:Peptide Fragments; D013744:Tetanus Toxin; D014612:Vaccines; D051844:alpha-Synuclein
keywords: B cell epitope of α-synuclein; Epitope vaccine; Immunotherapy; Parkinson's and Alzheimer's diseases; T cell epitope of tetanus toxin