title: Evaluation of an α synuclein sensitized dendritic cell based vaccine in a transgenic mouse model of Parkinson disease.
abstract: In order to develop a cell-based vaccine against the Parkinson disease (PD) associated protein α-synuclein (α-Syn) 3 peptides were synthesized based upon predicted B cell epitopes within the full length α-Syn protein sequence. These peptide fragments as well as the full length recombinant human α-Syn (rh- α-Syn) protein were used to sensitize mouse bone marrow-derived dendritic cells (DC) ex vivo, followed by intravenous delivery of these sensitized DCs into transgenic (Tg) mice expressing the human A53T variant of α-Syn. ELISA analysis and testing of behavioral locomotor function by rotometry were performed on all mice after the 5th vaccination as well as just prior to euthanasia. The results indicated that vaccination with peptide sensitized DCs (PSDC) as well as DCs sensitized by rh-α-Syn induced specific anti-α-Syn antibodies in all immunized mice. In terms of rotometry performance, a measure of locomotor activity correlated to brain dopamine levels, mice vaccinated with PSDC or rh- α-Syn sensitized DCs performed significantly better than non-vaccinated Tg control mice during the final assessment (i.e. at 17 months of age) before euthanasia. As well, measurement of levels of brain IL-1α, a cytokine hypothesized to be associated with neuroinflammation, demonstrated that this proinflammatory molecule was significantly reduced in the PSDC and rh- α-Syn sensitized DC vaccinated mice compared to the non-vaccinated Tg control group. Overall, α-Syn antigen-sensitized DC vaccination was effective in generating specific anti- α-Syn antibodies and improved locomotor function without eliciting an apparent general inflammatory response, indicating that this strategy may be a safe and effective treatment for PD.
authors.affiliation: a Department of Molecular Medicine ; University of South Florida; Morsani College of Medicine ; Tampa , FL USA.
authors.forename: Kenneth E
authors.initials: KE
authors.lastname: Ugen
authors.forename: Xiaoyang
authors.initials: X
authors.lastname: Lin
authors.forename: Ge
authors.initials: G
authors.lastname: Bai
authors.forename: Zhanhua
authors.initials: Z
authors.lastname: Liang
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Cai
authors.forename: Kunyun
authors.initials: K
authors.lastname: Li
authors.forename: Shijie
authors.initials: S
authors.lastname: Song
authors.forename: Chuanhai
authors.initials: C
authors.lastname: Cao
authors.forename: Juan
authors.initials: J
authors.lastname: Sanchez-Ramos
mesh_terms: D000818:Animals; D064987:Cell- and Tissue-Based Therapy / Q000379:methods; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009043:Motor Activity / Q000502:physiology; D010300:Parkinson Disease / Q000503:physiopathology / Q000517:prevention & control* / Q000628:therapy; D014612:Vaccines / Q000276:immunology*; D051844:alpha-Synuclein / Q000235:genetics / Q000378:metabolism*
chemical_list: D014612:Vaccines; D051844:alpha-Synuclein
keywords: B cell epitopes; Parkinson disease; antigen; cell therapy; dendritic cells; peptide; transgenic mice; α-synuclein