Liu Dong-Qun, Lu Shuai, Zhang Lun, Huang Ya-Ru, Ji Mei, Sun Xiao-Ying, Liu Xiao-Ge, Liu Rui-Tian
National Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China.
School of Chemical Engineering, University of Chinese Academy of Science, Beijing 100049, China.
Vaccines (Basel). 2020 Jul 1;8(3):351. doi: 10.3390/vaccines8030351.
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.
专注于减轻淀粉样β（Aβ）负担的免疫疗法是治疗阿尔茨海默病（AD）的一种有前景的治疗策略。许多关于AD免疫疗法的临床研究由于安全性和有效性低而失败，这就需要一种高效的AD疫苗，既能诱导足够的抗体滴度又能避免副作用。在此，我们设计了一种基于酵母的疫苗Y-5A15，它由五个拷贝的Aβ1-15展示在酵母细胞壁表面组成，我们对APP/PS1小鼠进行了三次皮下免疫接种。我们的结果表明Y-5A15显著增强了Aβ表位的免疫原性，并在AD小鼠中引发了针对Aβ的高抗体滴度。重要的是，Y-5A15疫苗接种成功降低了Aβ水平、斑块负担和胶质细胞活化，挽救了突触缺陷，并显著改善了APP/PS1转基因小鼠的记忆和认知衰退，表明基于酵母的Aβ表位疫苗在治疗AD方面具有有前景的效力。
