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Improved synaptic and cognitive function in aged 3 × Tg-AD mice with reduced amyloid-β after immunotherapy with a novel recombinant 6Aβ15-TF chimeric vaccine
Clinical Immunology ( IF 8.6 ) Pub Date : 2018-05-24 , DOI: 10.1016/j.clim.2018.05.005
Yun-Zhou Yu , Qing-Li Li , Hai-Chao Wang , Si Liu , Xiao-Bin Pang , Qing Xu , Xiao-Wei Zhou , Pei-Tang Huang

Alzheimer's disease (AD) is the most common progressive neurodegenerative disorder impairing memory and cognition. In this study, we describe the immunogenicity and protective efficacy of the novel recombinant 6Aβ15-TF chimeric antigen as a subunit protein vaccine for AD. Recombinant 6Aβ15-TF chimeric vaccine induced strong Aβ-specific humoral immune responses without Aβ-specific T cell immunity in C57/BL6 and 3 × Tg-AD mice at different ages. As an early immunotherapy model for AD, this vaccine induced high titers of long-lasting anti-Aβ42 antibodies in aged 3 × Tg-AD mice, which led to improve behavioral performance and markedly reduced the levels of insoluble and soluble Aβ and Aβ oligomers. In agreement with these findings, immunotherapy with 6Aβ15-TF prevented the Aβ-induced decrease of presynaptic and postsynaptic proteins in aged 3 × Tg-AD mice. Our results suggest that this novel and highly immunogenic recombinant 6Aβ15-TF chimeric vaccine provides neuroprotection in AD mice and can be considered an effective AD candidate vaccine.



中文翻译:

新型重组6Aβ15-TF嵌合疫苗免疫治疗后3号Tg-AD衰老的淀粉样蛋白-β降低的小鼠的突触和认知功能得到改善

阿尔茨海默氏病(AD)是最常见的进行性神经退行性疾病,会损害记忆力和认知能力。在这项研究中,我们描述了新型重组6Aβ15-TF嵌合抗原作为AD亚单位蛋白疫苗的免疫原性和保护功效。重组6Aβ15-TF嵌合疫苗可在不同年龄的C57 / BL6和3×Tg-AD小鼠中诱导强Aβ特异性体液免疫反应,而无Aβ特异性T细胞免疫。作为AD的早期免疫治疗模型,该疫苗在3只Tg-AD老年小鼠中诱导了高滴度的长效抗Aβ42抗体,从而改善了行为表现,并显着降低了不溶性和可溶性Aβ和Aβ寡聚体的水平。与这些发现一致,6Aβ15-TF免疫疗法可防止Aβ诱导的3×Tg-AD老年小鼠的突触前和突触后蛋白减少。我们的结果表明,这种新颖且具有高度免疫原性的重组6Aβ15-TF嵌合疫苗可为AD小鼠提供神经保护作用,可以认为是一种有效的AD候选疫苗。

更新日期:2018-05-24
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