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000187170 1001_ $$0P:(DE-HGF)0$$aMandler, M.$$b0
000187170 245__ $$aTailoring the Antibody Response to Aggregated Aß Using Novel Alzheimer-Vaccines
000187170 260__ $$aLawrence, Kan.$$bPLoS$$c2015
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000187170 520__ $$aRecent 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.
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000187170 7001_ $$0P:(DE-HGF)0$$aSantic, Radmila$$b1
000187170 7001_ $$0P:(DE-HGF)0$$aGruber, Petra$$b2
000187170 7001_ $$0P:(DE-Juel1)131993$$aCinar, Yeliz$$b3$$ufzj
000187170 7001_ $$0P:(DE-HGF)0$$aPichler, Dagmar$$b4
000187170 7001_ $$0P:(DE-HGF)0$$aFunke, Susanne Aileen$$b5
000187170 7001_ $$0P:(DE-Juel1)132029$$aWillbold, Dieter$$b6$$ufzj
000187170 7001_ $$0P:(DE-HGF)0$$aSchneeberger, Achim$$b7$$eCorresponding Author
000187170 7001_ $$0P:(DE-HGF)0$$aSchmidt, Walter$$b8
000187170 7001_ $$0P:(DE-HGF)0$$aMattner, Frank$$b9
000187170 773__ $$0PERI:(DE-600)2267670-3$$a10.1371/journal.pone.0115237$$gVol. 10, no. 1, p. e0115237 -$$n1$$pe0115237 -$$tPLoS one$$v10$$x1932-6203$$y2015
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