Yeast-Based Aβ1-15 Vaccine Elicits Strong Immunogenicity and Attenuates Neuropathology and Cognitive Deficits in Alzheimer's Disease Transgenic Mice.
Yeast-Based Aβ1-15 Vaccine Elicits Strong Immunogenicity and Attenuates Neuropathology and Cognitive Deficits in Alzheimer's Disease Transgenic Mice.
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DOI：
10.3390/vaccines8030351
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发表时间：
2020-07-01
期刊：
影响因子：
7.8
通讯作者：
Liu RT
中科院分区：
文献类型：
--
作者：
Liu DQ;Lu S;Zhang L;Huang YR;Ji M;Sun XY;Liu XG;Liu RT
专注于减少淀粉样蛋白 (Aβ) 负担的免疫疗法是治疗阿尔茨海默病 (AD) 的一种有前途的治疗策略。许多关于AD免疫疗法的临床研究因安全性和有效性低而失败，需要一种高效的AD疫苗，能够诱导足够的抗体滴度，同时避免副作用。在这里，我们设计了一种基于酵母的疫苗Y-5A15，其包含在酵母细胞壁表面展示的5个拷贝的Aβ1-15，并对APP/PS1小鼠进行皮下免疫3次。我们的结果表明，Y-5A15 显着增强了 AD 小鼠中 Aβ 表位的免疫原性并引发了针对 Aβ 的高抗体滴度。重要的是，Y-5A15 疫苗接种成功降低了 APP/PS1 转基因小鼠的 Aβ 水平、斑块负担和神经胶质活化，挽救了突触缺陷，并显着改善了记忆和认知能力下降，这表明基于酵母的 Aβ 表位疫苗具有治疗 AD 的良好效力。
Immunotherapy focusing on reducing the amyloid-beta (Aβ) burden is a promising treatment strategy for Alzheimer’s disease (AD). Many clinical studies on AD immunotherapies have failed due to low safety and efficacy, calling for a highly potent AD vaccine which induces sufficient antibody titer while avoiding side effects. Here, we designed a yeast-based vaccine Y-5A15 comprising five copies of Aβ1-15 displayed on the surface of yeast cell wall, and we subcutaneously immunized APP/PS1 mice three times. Our results demonstrated that the Y-5A15 remarkably enhanced the Aβ epitope immunogenicity and elicited high antibody titers against Aβ in AD mice. Importantly, Y-5A15 vaccination successfully reduced Aβ levels, plaque burden and glial activation, rescued synaptic deficits and significantly ameliorated memory and cognitive decline in APP/PS1 transgenic mice, suggesting that the yeast-based Aβ epitope vaccine has a promising potency for the treatment of AD.
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DOI：
10.3233/jad-179941
发表时间：
2018
期刊：
Journal of Alzheimer's disease : JAD
影响因子：
--
作者：
Cline EN;Bicca MA;Viola KL;Klein WL
通讯作者：
Klein WL
影响因子：
25
作者：
Cleary, JP;Walsh, DM;Ashe, KH
通讯作者：
Ashe, KH
影响因子：
3.7
作者：
Mandler M;Santic R;Gruber P;Cinar Y;Pichler D;Funke SA;Willbold D;Schneeberger A;Schmidt W;Mattner F
通讯作者：
Mattner F
影响因子：
168.9
作者：
Holmes, Clive;Boche, Delphine;Nicoll, James A. R.
通讯作者：
Nicoll, James A. R.
DOI：
10.1073/pnas.95.11.6448
发表时间：
1998-05-26
影响因子：
11.1
作者：
Lambert, MP;Barlow, AK;Klein, WL
通讯作者：
Klein, WL