Immune shaping and the development of Alzheimer's disease vaccines.
Immune shaping and the development of Alzheimer's disease vaccines.
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DOI：
10.1126/sageke.2005.46.pe35
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发表时间：
2005-11-16
期刊：
影响因子：
--
通讯作者：
Bowers, William J
中科院分区：
文献类型：
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作者：
Federoff, Howard J;Bowers, William J
鉴于阿尔茨海默病（AD）造成的情感，社会和经济破坏，必须设计有效的治疗方法来改善这种目前无法治愈的疾病。已经开发了基于疫苗的方法来靶向和消除淀粉样蛋白β（Abeta），淀粉样蛋白β是与AD发病机制有关的关键肽。AD小鼠模型的临床前成功为基于Abeta的疫苗的临床应用创造了兴奋和动力。引发针对自身肽（即由生物体本身产生的肽）的免疫反应，如Abeta，具有在接种疫苗的个体中诱导自身免疫和炎症的潜力，这是在最近的临床试验中招募的多名患者中证实的警告。这些临床不良事件似乎掩盖了这些和其他接种疫苗的患者中有趣的行为稳定和Abeta负荷的改变，从而说明了AD免疫治疗的潜力。了解疫苗降低AD脑中Abeta负荷的机制和免疫应答的类型，以及开发促进调节引发的免疫应答的疫苗递送新模式，无疑将导致新一代有效的Abeta免疫治疗药物具有改善的安全性。
Given the emotional, social, and financial devastation wrought by Alzheimer's disease (AD), it is imperative that effective therapeutics be devised to ameliorate this presently incurable disorder. Vaccine-based approaches have been developed to target and eliminate amyloid beta (Abeta), a key peptide implicated in AD pathogenesis. Preclinical successes in AD mouse models created excitement and impetus for the clinical application of an Abeta-based vaccine. Eliciting immune responses against a self-peptide (that is, a peptide produced by the organism itself), such as Abeta, carries with it the potential to induce autoimmune and inflammatory conditions in the vaccinated individual, a caveat borne out in multiple patients enrolled as part of a recent clinical trial. These clinical adverse events seemingly overshadowed interesting behavioral stabilization and alterations of Abeta burden in these and other vaccinated patients, thus speaking to the potential of immunotherapy for AD. Understanding the mechanisms by which vaccines reduce Abeta burden in AD brain and the types of immune responses raised, as well as developing new modalities of vaccine delivery that facilitate the modulation of elicited immune responses, will undoubtedly lead to a new generation of efficacious Abeta immunotherapeutics with improved safety profiles.