Tailoring the antibody response to aggregated Ass using novel Alzheimer-vaccines.

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Mandler M, Santic R, Gruber P, Cinar Y, Pichler D, Funke SA, Willbold D, Schneeberger A, Schmidt W, Mattner F

Tailoring the antibody response to aggregated Ass using novel Alzheimer-vaccines.

PLoS One. 2015 Jan 22;10(1):e0115237. doi: 10.1371/journal.pone.0115237. eCollection 2015.

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25611858 [ View in PubMed
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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 Abeta1-6, 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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