Epitopes described in "DNA immunization against amyloid beta 42 has high potential as safe therapy for Alzheimer's disease as it diminishes antigen-specific Th1 and Th17 cell proliferation."

Article Authors:Doris Lambracht-Washington; Bao-Xi Qu; Min Fu; Larry D Anderson Jr; Olaf Stüve; Todd N Eagar; Roger N Rosenberg
Article Title:DNA immunization against amyloid beta 42 has high potential as safe therapy for Alzheimer's disease as it diminishes antigen-specific Th1 and Th17 cell proliferation.
Reference Detail
Reference ID:1022301
Abstract:The pathogenesis of Alzheimer's disease (AD) has been strongly associated with the accumulation of amyloid beta (A) peptides in brain, and immunotherapy targeting A provides potential for AD prevention. A clinical trial in which AD patients were immunized with A42 peptide was stopped when 6% of participants showed meningoencephalitis, apparently due to an inflammatory Th1 immune response. Previously, we and other have shown that A42 DNA vaccination via gene gun generates a Th2 cellular immune response, which was shown by analyses of the respective antibody isotype profiles. We also determined that in vitro T cell proliferation in response to A42 peptide re-stimulation was absent in DNA A42 trimer-immunized mice when compared to A42 peptide-immunized mice. To further characterize this observation prospectively and longitudinally, we analyzed the immune response in wild-type mice after vaccination with A42 trimer DNA and A42 peptide with Quil A adjuvant. Wild-type mice were immunized with short-term (1-3× vaccinations) or long-term (6× vacinations) immunization strategies. Antibody titers and isotype profiles of the A42 specific antibodies, as well as cytokine profiles and cell proliferation studies from this longitudinal study were determined. Sufficient antibody titers to effectively reduce A42, but an absent T cell proliferative response and no IFN or IL-17 secretion after A42 DNA trimer immunization minimizes the risk of inflammatory activities of the immune system towards the self antigen A42 in brain. Therefore, A42 DNA trimer immunization has a high probability to be effective and safe to treat patients with early AD.
Affiliations:Department of Neurology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9036, USA.
Reference Type:Literature
PubMed ID:21625960
Journal:Cell Mol Neurobiol
Journal Volume:31
Article Pages:867-74
Journal ISSN:0272-4340
Article Chemical List:5-(6)-carboxyfluorescein diacetate succinimidyl ester;Amyloid beta-Peptides;Cytokines;Epitopes;Fluoresceins;Succinimides;DNA
Article MeSH List:Alzheimer Disease(immunology; therapy); Amyloid beta-Peptides(immunology); Animals; Cell Proliferation; Cytokines(secretion); DNA(immunology); Enzyme-Linked Immunospot Assay; Epitopes(immunology); Fluoresceins; Immunity, Humoral; Immunization; Mice; Succinimides; Th1 Cells(cytology; immunology); Th17 Cells(cytology; immunology)
Curation Last Updated:2015-07-30 20:40:39