TY  - JOUR
AU  - Mandler, M.
AU  - Santic, Radmila
AU  - Gruber, Petra
AU  - Cinar, Yeliz
AU  - Pichler, Dagmar
AU  - Funke, Susanne Aileen
AU  - Willbold, Dieter
AU  - Schneeberger, Achim
AU  - Schmidt, Walter
AU  - Mattner, Frank
TI  - Tailoring the Antibody Response to Aggregated Aß Using Novel Alzheimer-Vaccines
JO  - PLoS one
VL  - 10
IS  - 1
SN  - 1932-6203
CY  - Lawrence, Kan.
PB  - PLoS
M1  - FZJ-2015-00844
SP  - e0115237 -
PY  - 2015
AB  - 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.
LB  - PUB:(DE-HGF)16
UR  - <Go to ISI:>//WOS:000348562900006
DO  - DOI:10.1371/journal.pone.0115237
UR  - https://juser.fz-juelich.de/record/187170
ER  -