Department of Molecular Immunology, Institute for Molecular Medicine, Huntington Beach, CA 92647, USA.
J Transl Med. 2011 Aug 1;9:127. doi: 10.1186/1479-5876-9-127.
Numerous pre-clinical studies and clinical trials demonstrated that induction of antibodies to the β-amyloid peptide of 42 residues (Aβ42) elicits therapeutic effects in Alzheimer's disease (AD). However, an active vaccination strategy based on full length Aβ42 is currently hampered by elicitation of T cell pathological autoreactivity. We attempt to improve vaccine efficacy by creating a novel chimeric flu vaccine expressing the small immunodominant B cell epitope of Aβ42. We hypothesized that in elderly people with pre-existing memory Th cells specific to influenza this dual vaccine will simultaneously boost anti-influenza immunity and induce production of therapeutically active anti-Aβ antibodies.
Plasmid-based reverse genetics system was used for the rescue of recombinant influenza virus containing immunodominant B cell epitopes of Aβ42 (Aβ1-7/10).
Two chimeric flu viruses expressing either 7 or 10 aa of Aβ42 (flu-Aβ1-7 or flu-Aβ1-10) were generated and tested in mice as conventional inactivated vaccines. We demonstrated that this dual vaccine induced therapeutically potent anti-Aβ antibodies and anti-influenza antibodies in mice.
We suggest that this strategy might be beneficial for treatment of AD patients as well as for prevention of development of AD pathology in pre-symptomatic individuals while concurrently boosting immunity against influenza.
大量的临床前研究和临床试验表明，诱导针对β-淀粉样肽 42 个残基（Aβ42）的抗体可在阿尔茨海默病（AD）中发挥治疗作用。然而，目前基于全长 Aβ42 的主动免疫接种策略受到 T 细胞病理性自身反应性的影响。我们试图通过创建一种表达 Aβ42 小免疫显性 B 细胞表位的新型嵌合流感疫苗来提高疫苗的疗效。我们假设在老年人中，流感病毒存在针对预先存在的记忆 T 细胞的特异性 Th 细胞，这种双重疫苗将同时增强抗流感免疫力并诱导产生治疗性的抗 Aβ 抗体。
使用基于质粒的反向遗传学系统拯救含有 Aβ42 免疫显性 B 细胞表位的重组流感病毒（Aβ1-7/10）。
生成并测试了两种表达 Aβ42 的 7 或 10 个氨基酸（flu-Aβ1-7 或 flu-Aβ1-10）的嵌合流感病毒作为常规灭活疫苗。我们证明了这种双重疫苗可在小鼠中诱导产生治疗性的抗 Aβ 抗体和抗流感抗体。
我们认为这种策略可能对 AD 患者的治疗以及预防无症状个体 AD 病理的发展有益，同时增强对流感的免疫力。
