title: Tailoring the antibody response to aggregated Aß using novel Alzheimer-vaccines.
abstract: Recent evidence suggests Alzheimer-Disease (AD) to be driven by aggregated Aß. Capitalizing on the mechanism of molecular mimicry and applying several selection layers, we screened peptide libraries for moieties inducing antibodies selectively reacting with Aß-aggregates. The technology identified a pool of peptide candidates; two, AFFITOPES AD01 and AD02, were assessed as vaccination antigens and compared to Aβ1-6, the targeted epitope. When conjugated to Keyhole Limpet Hemocyanin (KLH) and adjuvanted with aluminum, all three peptides induced Aß-targeting antibodies (Abs). In contrast to Aß1-6, AD01- or AD02-induced Abs were characterized by selectivity for aggregated forms of Aß and absence of reactivity with related molecules such as Amyloid Precursor Protein (APP)/ secreted APP-alpha (sAPPa). Administration of AFFITOPE-vaccines to APP-transgenic mice was found to reduce their cerebral amyloid burden, the associated neuropathological alterations and to improve their cognitive functions. Thus, the AFFITOME-technology delivers vaccines capable of inducing a distinct Ab response. Their features may be beneficial to AD-patients, a hypothesis currently tested within a phase-II-study.
authors.affiliation: AFFiRiS AG, Karl-Farkas-Gasse 22, A-1030, Vienna, Austria.
authors.forename: Markus
authors.initials: M
authors.lastname: Mandler
authors.affiliation: AFFiRiS AG, Karl-Farkas-Gasse 22, A-1030, Vienna, Austria.
authors.forename: Radmila
authors.initials: R
authors.lastname: Santic
authors.affiliation: AFFiRiS AG, Karl-Farkas-Gasse 22, A-1030, Vienna, Austria.
authors.forename: Petra
authors.initials: P
authors.lastname: Gruber
authors.affiliation: Institute for Structural Biochemistry (Institute of Complex Systems 6), Forschungszentrum Jülich, 52425, Jülich, Germany.
authors.forename: Yeliz
authors.initials: Y
authors.lastname: Cinar
authors.affiliation: AFFiRiS AG, Karl-Farkas-Gasse 22, A-1030, Vienna, Austria.
authors.forename: Dagmar
authors.initials: D
authors.lastname: Pichler
authors.affiliation: Institute for Structural Biochemistry (Institute of Complex Systems 6), Forschungszentrum Jülich, 52425, Jülich, Germany.
authors.forename: Susanne Aileen
authors.initials: SA
authors.lastname: Funke
authors.affiliation: Institute for Structural Biochemistry (Institute of Complex Systems 6), Forschungszentrum Jülich, 52425, Jülich, Germany.
authors.forename: Dieter
authors.initials: D
authors.lastname: Willbold
authors.affiliation: AFFiRiS AG, Karl-Farkas-Gasse 22, A-1030, Vienna, Austria.
authors.forename: Achim
authors.initials: A
authors.lastname: Schneeberger
authors.affiliation: AFFiRiS AG, Karl-Farkas-Gasse 22, A-1030, Vienna, Austria.
authors.forename: Walter
authors.initials: W
authors.lastname: Schmidt
authors.affiliation: AFFiRiS AG, Karl-Farkas-Gasse 22, A-1030, Vienna, Austria.
authors.forename: Frank
authors.initials: F
authors.lastname: Mattner
mesh_terms: D000544:Alzheimer Disease / Q000276:immunology / Q000628:therapy*; D023582:Alzheimer Vaccines / Q000276:immunology / Q000627:therapeutic use*; D016229:Amyloid beta-Peptides / Q000276:immunology*; D000818:Animals; D000906:Antibodies / Q000276:immunology*; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D019151:Peptide Library
chemical_list: D023582:Alzheimer Vaccines; D016229:Amyloid beta-Peptides; D000906:Antibodies; D019151:Peptide Library