Immunogenicity of epitope vaccines targeting different B cell antigenic determinants of human α-synuclein: Feasibility study
| Autor: | Anahit Ghochikyan, Michael G. Agadjanyan, Hayk Davtyan, Irina Petrushina, Arpine Davtyan, Tommy Saing, David H. Cribbs, Armine Hovakimyan |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Lewy Body Disease
animal diseases Biology Article Epitope Mice Tetanus Toxin Antigen Neurites medicine Animals Humans B cell Vaccines Dementia with Lewy bodies General Neuroscience Immunogenicity Vaccination Neurodegeneration Brain medicine.disease Virology Peptide Fragments nervous system diseases medicine.anatomical_structure nervous system Immunization Antibody Formation Immunology alpha-Synuclein biology.protein Epitopes B-Lymphocyte Feasibility Studies Female Lewy Bodies Antibody |
| Zdroj: | Neuroscience Letters. 560:86-91 |
| ISSN: | 0304-3940 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect