Davtyan Hayk, Petrushina Irina, Ghochikyan Anahit
Department of Molecular Immunology, Institute for Molecular Medicine, 16371 Gothard Street, Huntington Beach, CA, 92647, USA.
Methods Mol Biol. 2014;1143:259-81. doi: 10.1007/978-1-4939-0410-5_16.
Active immunotherapy for Alzheimer's disease (AD) is aimed to induce antibodies specific to amyloid-beta (Aβ) that are capable to reduce the level of Aβ in the CNS of Alzheimer's disease patients. First clinical trial AN-1792 that was based on vaccination with full-length Aβ42 showed that safe and effective AD vaccine should induce high titers of anti-Aβ antibodies without activation of harmful autoreactive T cells. Replacement of self-T cell epitope with foreign epitope, keeping self-B cell epitope intact, may allow to induce high titers of anti-Aβ antibodies while avoiding the activation of T cells specific to Aβ. Here we describe the protocols for evaluation of AD DNA- or multiple antigenic peptide (MAP)-based epitope vaccines composed of Aβ(1-11) B cell epitope fused to synthetic T cell epitope PADRE (Aβ(1-11)-PADRE). All protocols could be used for testing any epitope vaccine constructed in your lab and composed of other T cell epitopes using the appropriate peptides in tests for evaluation of humoral and cellular immune responses.
阿尔茨海默病（AD）的主动免疫疗法旨在诱导针对β-淀粉样蛋白（Aβ）的特异性抗体，这些抗体能够降低阿尔茨海默病患者中枢神经系统中Aβ的水平。首个基于全长Aβ42疫苗接种的临床试验AN-1792表明，安全有效的AD疫苗应诱导高滴度的抗Aβ抗体，而不激活有害的自身反应性T细胞。用外来表位替换自身T细胞表位，同时保持自身B细胞表位完整，可能有助于诱导高滴度的抗Aβ抗体，同时避免激活Aβ特异性T细胞。在此，我们描述了评估基于AD DNA或多抗原肽（MAP）的表位疫苗的方案，该疫苗由与合成T细胞表位PADRE融合的Aβ（1-11）B细胞表位组成（Aβ（1-11）-PADRE）。所有方案均可用于测试您实验室构建的、由其他T细胞表位组成的任何表位疫苗，在评估体液和细胞免疫反应的测试中使用适当的肽。
