Maier Marcel, Seabrook Timothy J, Lemere Cynthia A
Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Neurodegener Dis. 2005;2(5):267-72. doi: 10.1159/000090367.
Active amyloid beta (A beta) vaccination has been shown to be effective in clearing cerebral A beta and improving cognitive function in mouse models of Alzheimer's disease. However, an A beta vaccine clinical trial was suspended after meningoencephalitis was detected in a subset of subjects. Passive immunization has been suggested to be a safer alternative to active A beta immunization but there are reports of increased risk of microhemorrhages associated with its administration in aged beta-amyloid precursor protein transgenic mice bearing abundant vascular amyloid deposition. In addition, the cost may be prohibitive for large-scale clinical use. Therefore, we are designing novel A beta immunogens that encompass the B cell epitope of A beta but lack the T cell-reactive sites. These immunogens induced the production of A beta-specific antibodies in the absence of an A beta-specific cellular immune response in wild-type mice and are being tested in beta-amyloid precursor protein transgenic mice. These data together with published reports from several other groups suggest that a safe, active A beta vaccine is a tenable goal.
在阿尔茨海默病小鼠模型中，活性β淀粉样蛋白（Aβ）疫苗已被证明可有效清除脑内Aβ并改善认知功能。然而，在部分受试者中检测到脑膜脑炎后，一项Aβ疫苗临床试验被暂停。被动免疫被认为是活性Aβ免疫的一种更安全替代方法，但有报道称，在携带大量血管淀粉样沉积的老年β淀粉样前体蛋白转基因小鼠中，被动免疫给药会增加微出血风险。此外，其成本可能使大规模临床应用望而却步。因此，我们正在设计新型Aβ免疫原，这些免疫原包含Aβ的B细胞表位，但缺乏T细胞反应位点。这些免疫原在野生型小鼠中诱导产生Aβ特异性抗体，且无Aβ特异性细胞免疫反应，目前正在β淀粉样前体蛋白转基因小鼠中进行测试。这些数据以及其他几个研究小组发表的报告表明，一种安全的活性Aβ疫苗是一个可行的目标。
