Beijing Institute of Biotechnology, 20 Dongdajie Street, Fengtai District, Beijing, 100071, China.
Institute of Life Science and Biotechnology, Beijing Jiaotong University, Beijing, 100044, China.
J Neuroimmune Pharmacol. 2016 Dec;11(4):657-668. doi: 10.1007/s11481-016-9678-5. Epub 2016 May 5.
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by a progressive amyloid-β accumulation, loss of cognitive abilities, and synaptic alterations. Given the remarkable recovery of cognition in AD models of targeting-Aβ immunotherapy, we sought to determine the molecular correlate(s) associated with improvement. We evaluated the efficacy of a recombinant chimeric 6Aβ15-T antigen formulated with alum adjuvant as a novel Aβ B-cell epitope vaccine (rCV01) in 3 × Tg-AD mice. rCV01 elicited robust Th2-polarized Aβ-specific antibodies without autoimmune T cell responses in 3 × Tg-AD mice. The long-lasting anti-Aβ42 antibodies were associated with markedly reduced AD-like pathology, enhanced synaptic function, and improved cognitive performance in aged 3 × Tg-AD mice. This is the first report to provide one hypothesis for the improved outcomes following vaccination is a reduction in the levels of active calpain in rCV01-immunized AD mice, which is likely attributable to preventing dynamin 1 and PSD-95 degradation allowing functional recovery of cognition. rCV01 is a highly immunogenic recombinant chimeric 6Aβ15-T vaccine that shows clear neuroprotective properties in preclinical mouse models of AD and is a candidate for an effective AD vaccine.
阿尔茨海默病（AD）是一种神经退行性疾病，其特征是淀粉样蛋白-β的进行性积累、认知能力的丧失和突触改变。鉴于靶向 Aβ 免疫疗法的 AD 模型中认知能力的显著恢复，我们试图确定与改善相关的分子相关性。我们评估了用明矾佐剂配制的重组嵌合 6Aβ15-T 抗原作为新型 Aβ B 细胞表位疫苗（rCV01）在 3×Tg-AD 小鼠中的疗效。rCV01 在 3×Tg-AD 小鼠中引发了强烈的 Th2 极化的 Aβ 特异性抗体，而没有自身免疫 T 细胞反应。持久的抗 Aβ42 抗体与 AD 样病理的明显减少、突触功能的增强以及老年 3×Tg-AD 小鼠认知表现的改善相关。这是第一个提供假设的报告，即疫苗接种后的改善结果是 rCV01 免疫 AD 小鼠中活性钙蛋白酶水平降低，这可能归因于阻止了裂孔形成蛋白 1 和 PSD-95 的降解，从而允许认知功能的恢复。rCV01 是一种高度免疫原性的重组嵌合 6Aβ15-T 疫苗，在 AD 的临床前小鼠模型中表现出明显的神经保护特性，是一种有效的 AD 疫苗候选物。
