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MultiTEP platform-based DNA vaccines for alpha-synucleinopathies: preclinical evaluation of immunogenicity and therapeutic potency.
Davtyan, Hayk; Zagorski, Karen; Petrushina, Irina; Kazarian, Konstantin; Goldberg, Natalie R S; Petrosyan, Janet; Blurton-Jones, Mathew; Masliah, Eliezer; Cribbs, David H; Agadjanyan, Michael G; Ghochikyan, Anahit.
Afiliação
  • Davtyan H; Department of Molecular Immunology, Institute for Molecular Medicine, Huntington Beach, CA, USA; Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA, USA.
  • Zagorski K; Department of Molecular Immunology, Institute for Molecular Medicine, Huntington Beach, CA, USA.
  • Petrushina I; Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA, USA.
  • Kazarian K; Department of Molecular Immunology, Institute for Molecular Medicine, Huntington Beach, CA, USA.
  • Goldberg NRS; Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA, USA; Department of Neurobiology and Behavior, University of California, Irvine, Irvine, CA, USA; Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, Irvine, CA, USA.
  • Petrosyan J; Department of Molecular Immunology, Institute for Molecular Medicine, Huntington Beach, CA, USA.
  • Blurton-Jones M; Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA, USA; Department of Neurobiology and Behavior, University of California, Irvine, Irvine, CA, USA; Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, Irvine, CA, USA.
  • Masliah E; Department of Neurosciences, University of California, San Diego, La Jolla, CA, USA; Department of Pathology, University of California, San Diego, La Jolla, CA, USA.
  • Cribbs DH; Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA, USA.
  • Agadjanyan MG; Department of Molecular Immunology, Institute for Molecular Medicine, Huntington Beach, CA, USA; Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA, USA. Electronic address: magadjanyan@immed.org.
  • Ghochikyan A; Department of Molecular Immunology, Institute for Molecular Medicine, Huntington Beach, CA, USA. Electronic address: aghochikyan@immed.org.
Neurobiol Aging ; 59: 156-170, 2017 11.
Article em En | MEDLINE | ID: mdl-28870518
ABSTRACT
We have previously demonstrated that anti-beta amyloid DNA vaccine (AV-1959D) based on our proprietary MultiTEP platform technology is extremely immunogenic in mice, rabbits, and monkeys. Importantly, MultiTEP platform enables development of vaccines targeting pathological molecules involved in various neurodegenerative disorders. Taking advantage of the universality of MultiTEP platform, we developed DNA vaccines targeting 3 B-cell epitopes (amino acids [aa]85-99, aa109-126, and aa126-140) of human alpha-synuclein (hα-Syn) separately or all 3 epitopes simultaneously. All 4 DNA vaccines (1) generate high titers of anti-hα-Syn antibodies and (2) induce robust MultiTEP-specific T-helper cell responses without activation of potentially detrimental autoreactive anti-hα-Syn T-helper cells. Generated antibodies recognize misfolded hα-Syn produced by neuroblastoma cells, hα-Syn in the brain tissues of transgenic mouse strains and in the brain tissues of dementia with Lewy body cases. Based on these results, the most promising vaccine targeting 3 B-cell epitopes of hα-Syn simultaneously (PV-1950D) has been chosen for ongoing preclinical assessment in mouse models of hα-Syn with the aim to translate it to the human clinical trials.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Epitopos de Linfócito B / Vacinas de DNA / Doenças Neurodegenerativas / Alfa-Sinucleína Limite: Animals / Female / Humans Idioma: En Ano de publicação: 2017 Tipo de documento: Article
Texto completo
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Epitopos de Linfócito B / Vacinas de DNA / Doenças Neurodegenerativas / Alfa-Sinucleína Limite: Animals / Female / Humans Idioma: En Ano de publicação: 2017 Tipo de documento: Article