Tailoring the antibody response to aggregated Aß using novel Alzheimer-vaccines.
Tailoring the antibody response to aggregated Aß using novel Alzheimer-vaccines.
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DOI：
10.1371/journal.pone.0115237
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Mattner F
中科院分区：
文献类型：
--
作者：
Mandler M;Santic R;Gruber P;Cinar Y;Pichler D;Funke SA;Willbold D;Schneeberger A;Schmidt W;Mattner F
最近的证据表明，阿尔茨海默病(AD)是由聚集的A？利用分子模拟的机制，应用几个选择层，我们筛选了部分诱导抗体与A？聚集体选择性反应的多肽文库。该技术确定了一组候选多肽；AFFITOPES AD01和AD02被评估为疫苗抗原，并与目标表位Aβ1-6进行比较。当三种多肽与Keyhole Limet血蓝蛋白(KLH)偶联并辅以铝时，均可诱导A？靶向抗体(Abs)。AD01或AD02诱导的单抗的特征是选择性地结合聚集形式，且不与淀粉样前体蛋白(APP)/分泌型APP-α(SAPA)等相关分子发生反应。研究发现，给APP转基因小鼠注射AFFITOPE疫苗可以减少它们的大脑淀粉样蛋白负担，减少相关的神经病理改变，并改善它们的认知功能。因此，AFFITOME技术提供了能够诱导不同抗体反应的疫苗。它们的特征可能对AD患者有利，这一假设目前在II期研究中得到验证。
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.
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影响因子：
5.4
作者：
Johansson, Ann-Sofi;Berglind-Dehlin, Fredrik;Lannfelt, Lars
通讯作者：
Lannfelt, Lars
影响因子：
16.2
作者：
Kamenetz, F;Tomita, T;Malinow, R
通讯作者：
Malinow, R
影响因子：
5.3
作者：
Comery, TA;Martone, RL;Marquis, KL
通讯作者：
Marquis, KL
影响因子：
11.4
作者：
Leyssen, M;Ayaz, D;Hassan, BA
通讯作者：
Hassan, BA
DOI：
10.1073/pnas.151261398
发表时间：
2001-07-17
影响因子：
11.1
作者：
DeMattos, RB;Bales, KR;Holtzman, DM
通讯作者：
Holtzman, DM