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@ARTICLE{Mandler:187170,
author = {Mandler, M. and Santic, Radmila and Gruber, Petra and
Cinar, Yeliz and Pichler, Dagmar and Funke, Susanne Aileen
and Willbold, Dieter and Schneeberger, Achim and Schmidt,
Walter and Mattner, Frank},
title = {{T}ailoring the {A}ntibody {R}esponse to {A}ggregated {A}ß
{U}sing {N}ovel {A}lzheimer-{V}accines},
journal = {PLoS one},
volume = {10},
number = {1},
issn = {1932-6203},
address = {Lawrence, Kan.},
publisher = {PLoS},
reportid = {FZJ-2015-00844},
pages = {e0115237 -},
year = {2015},
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.},
cin = {ICS-6},
ddc = {500},
cid = {I:(DE-Juel1)ICS-6-20110106},
pnm = {553 - Physical Basis of Diseases (POF3-553)},
pid = {G:(DE-HGF)POF3-553},
typ = {PUB:(DE-HGF)16},
UT = {WOS:000348562900006},
doi = {10.1371/journal.pone.0115237},
url = {https://juser.fz-juelich.de/record/187170},
}