{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,9]],"date-time":"2026-11-09T04:05:26Z","timestamp":1794197126269,"version":"4.8.0"},"reference-count":48,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2022,5,29]],"date-time":"2022-05-29T00:00:00Z","timestamp":1653782400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AG20241"],"award-info":[{"award-number":["R01AG20241"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01NS050895"],"award-info":[{"award-number":["R01NS050895"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U01AG060965"],"award-info":[{"award-number":["U01AG060965"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P30AG066519"],"award-info":[{"award-number":["P30AG066519"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"University of California, Irvine Alzheimer\u2019s Disease Research Center","award":["R01AG20241"],"award-info":[{"award-number":["R01AG20241"]}]},{"name":"University of California, Irvine Alzheimer\u2019s Disease Research Center","award":["R01NS050895"],"award-info":[{"award-number":["R01NS050895"]}]},{"name":"University of California, Irvine Alzheimer\u2019s Disease Research Center","award":["U01AG060965"],"award-info":[{"award-number":["U01AG060965"]}]},{"name":"University of California, Irvine Alzheimer\u2019s Disease Research Center","award":["P30AG066519"],"award-info":[{"award-number":["P30AG066519"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Parkinson\u2019s disease (PD) and dementia with Lewy bodies (DLB) are characterized by the aberrant accumulation of intracytoplasmic misfolded and aggregated \u03b1-synuclein (\u03b1-Syn), resulting in neurodegeneration associated with inflammation. The propagation of \u03b1-Syn aggregates from cell to cell is implicated in the spreading of pathological \u03b1-Syn in the brain and disease progression. We and others demonstrated that antibodies generated after active and passive vaccinations could inhibit the propagation of pathological \u03b1-Syn in the extracellular space and prevent\/inhibit disease\/s in the relevant animal models. We recently tested the immunogenicity and efficacy of four DNA vaccines on the basis of the universal MultiTEP platform technology in the DLB\/PD mouse model. The antibodies generated by these vaccines efficiently reduced\/inhibited the accumulation of pathological \u03b1-Syn in the different brain regions and improved the motor deficit of immunized female mice. The most immunogenic and preclinically effective vaccine, PV-1950D, targeting three B-cell epitopes of pathological \u03b1-Syn simultaneously, has been selected for future IND-enabling studies. However, to ensure therapeutically potent concentrations of \u03b1-Syn antibodies in the periphery of the vaccinated elderly, we developed a recombinant protein-based MultiTEP vaccine, PV-1950R\/A, and tested its immunogenicity in young and aged D-line mice. Antibody responses induced by immunizations with the PV-1950R\/A vaccine and its homologous DNA counterpart, PV-1950D, in a mouse model of PD\/DLB have been compared.<\/jats:p>","DOI":"10.3390\/ijms23116080","type":"journal-article","created":{"date-parts":[[2022,5,29]],"date-time":"2022-05-29T08:50:51Z","timestamp":1653814251000},"page":"6080","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Immunogenicity of MultiTEP-Platform-Based Recombinant Protein Vaccine, PV-1950R, Targeting Three B-Cell Antigenic Determinants of Pathological \u03b1-Synuclein"],"prefix":"10.3390","volume":"23","author":[{"given":"Karen","family":"Zagorski","sequence":"first","affiliation":[{"name":"Department of Molecular Immunology, Institute for Molecular Medicine, Huntington Beach, CA 92647, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gor","family":"Chailyan","sequence":"additional","affiliation":[{"name":"Department of Molecular Immunology, Institute for Molecular Medicine, Huntington Beach, CA 92647, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Armine","family":"Hovakimyan","sequence":"additional","affiliation":[{"name":"Department of Molecular Immunology, Institute for Molecular Medicine, Huntington Beach, CA 92647, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatevik","family":"Antonyan","sequence":"additional","affiliation":[{"name":"Department of Molecular Immunology, Institute for Molecular Medicine, Huntington Beach, CA 92647, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sepideh","family":"Kiani Shabestari","sequence":"additional","affiliation":[{"name":"Institute for Memory Impairments and Neurological Disorders, University of California Irvine, Irvine, CA 92697, USA"},{"name":"Sue and Bill Gross Stem Cell Research Center, University of California Irvine, Irvine, CA 92697, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina","family":"Petrushina","sequence":"additional","affiliation":[{"name":"Institute for Memory Impairments and Neurological Disorders, University of California Irvine, Irvine, CA 92697, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8554-6456","authenticated-orcid":false,"given":"Hayk","family":"Davtyan","sequence":"additional","affiliation":[{"name":"Institute for Memory Impairments and Neurological Disorders, University of California Irvine, Irvine, CA 92697, USA"},{"name":"Sue and Bill Gross Stem Cell Research Center, University of California Irvine, Irvine, CA 92697, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David H.","family":"Cribbs","sequence":"additional","affiliation":[{"name":"Institute for Memory Impairments and Neurological Disorders, University of California Irvine, Irvine, CA 92697, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathew","family":"Blurton-Jones","sequence":"additional","affiliation":[{"name":"Institute for Memory Impairments and Neurological Disorders, University of California Irvine, Irvine, CA 92697, USA"},{"name":"Sue and Bill Gross Stem Cell Research Center, University of California Irvine, Irvine, CA 92697, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eliezer","family":"Masliah","sequence":"additional","affiliation":[{"name":"Laboratory of Neurogenetics, National Institute of Aging, National Institute of Health, Bethesda, MD 20814, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael G.","family":"Agadjanyan","sequence":"additional","affiliation":[{"name":"Department of Molecular Immunology, Institute for Molecular Medicine, Huntington Beach, CA 92647, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anahit","family":"Ghochikyan","sequence":"additional","affiliation":[{"name":"Department of Molecular Immunology, Institute for Molecular Medicine, Huntington Beach, CA 92647, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1084\/jem.20112457","article-title":"Intracerebral inoculation of pathological alpha-synuclein initiates a rapidly progressive neurodegenerative alpha-synucleinopathy in mice","volume":"209","author":"Luk","year":"2012","journal-title":"J. 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