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Dementia with Lewy bodies (DLB) and Parkinson\u2019s disease (PD) are characterized by the aberrant accumulation of \u03b1-Syn intracytoplasmic Lewy body inclusions and dystrophic Lewy neurites resulting in neurodegeneration associated with inflammation. Cell to cell propagation of \u03b1-Syn aggregates is implicated in the progression of PD\/DLB, and high concentrations of anti-\u03b1-Syn antibodies could inhibit\/reduce the spreading of this pathological molecule in the brain. To ensure sufficient therapeutic concentrations of anti-\u03b1-Syn antibodies in the periphery and CNS, we developed four \u03b1-Syn DNA vaccines based on the universal MultiTEP platform technology designed especially for the elderly with immunosenescence. Here, we are reporting on the efficacy and immunogenicity of these vaccines targeting three B-cell epitopes of h\u03b1-Syn aa85\u201399 (PV-1947D), aa109\u2013126 (PV-1948D), aa126\u2013140 (PV-1949D) separately or simultaneously (PV-1950D) in a mouse model of synucleinopathies mimicking PD\/DLB. All vaccines induced high titers of antibodies specific to h\u03b1-Syn that significantly reduced PD\/DLB-like pathology in h\u03b1-Syn D line mice. The most significant reduction of the total and protein kinase resistant h\u03b1-Syn, as well as neurodegeneration, were observed in various brain regions of mice vaccinated with PV-1949D and PV-1950D in a sex-dependent manner. Based on these preclinical data, we selected the PV-1950D vaccine for future IND enabling preclinical studies and clinical development.<\/jats:p>","DOI":"10.1038\/s41541-021-00424-2","type":"journal-article","created":{"date-parts":[[2022,1,10]],"date-time":"2022-01-10T11:02:59Z","timestamp":1641812579000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["RETRACTED ARTICLE: Efficacy and immunogenicity of MultiTEP-based DNA vaccines targeting human \u03b1-synuclein: prelude for IND enabling studies"],"prefix":"10.1038","volume":"7","author":[{"given":"Changyoun","family":"Kim","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Armine","family":"Hovakimyan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Zagorski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatevik","family":"Antonyan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina","family":"Petrushina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8554-6456","authenticated-orcid":false,"given":"Hayk","family":"Davtyan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gor","family":"Chailyan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Hasselmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michiyo","family":"Iba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Adame","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward","family":"Rockenstein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1336-1951","authenticated-orcid":false,"given":"Marcell","family":"Szabo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7770-7157","authenticated-orcid":false,"given":"Mathew","family":"Blurton-Jones","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David H.","family":"Cribbs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anahit","family":"Ghochikyan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eliezer","family":"Masliah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9602-0406","authenticated-orcid":false,"given":"Michael G.","family":"Agadjanyan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,1,10]]},"reference":[{"key":"424_CR1","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1111\/neup.12691","volume":"40","author":"K Wakabayashi","year":"2020","unstructured":"Wakabayashi, K. 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