MUCOSAL ABETA VACCINATION; MODULATING THE IMMUNE RESPONSE

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。Aβ免疫疗法具有预防和可能治疗人类阿尔茨海默病(AD)的潜力。对基因工程AD小鼠模型的研究一直表明，Abeta疫苗在降低中枢Abeta和改善认知方面都有效，没有任何不良影响。然而，在大约6%的患者中，第一次人类临床试验因脑膜脑炎而停止；识别全长Abeta免疫原作为一种自身蛋白可能是导致这些不良事件的原因。非人灵长类动物，包括加勒比海扇贝(ChlorOcean Bus Athiiops)，与人类具有相同的淀粉样前体蛋白(APP)和Abeta，并有与年龄相关的脑斑块沉积。因此，它们可能成为研究Abeta清除和对Abeta疫苗免疫反应的较好动物模型。我们正在为认知功能的行为测试进行培训，并将在接下来的几个月内开始接种Abeta疫苗。我们的目标是表征一种新型Abeta疫苗的体液和细胞免疫反应，并确定S疫苗在降低神经系统内Abeta和改善认知方面的有效性。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Abeta immunotherapy has potential for preventing and possibly treating Alzheimer¿s disease (AD) in humans. Studies in genetically-engineered AD mouse models have consistently demonstrated efficacy of the Abeta vaccine both in lowering CNS Abeta and improving cognition without any adverse effects. However, the first human clinical trial was halted due to meningoencephalitis in approximately 6% of patients; recognition of the full-length Abeta immunogen as a self-protein may have attributed to these adverse events. Non-human primates, including Caribbean vervets (Chlorocebus aethiops), have the same amyloid precursor protein (APP) and Abeta as humans, and have age-related cerebral plaque deposition. Thus, they may serve as a better animal model for studying Abeta clearance and immune responses to Abeta vaccination. We are training vervets for behavioral testing of cognitive functions and will begin Abeta vaccination in the next several months. Our goals are to characterize the humoral and cellular immune responses to a novel Abeta vaccine and to determine the vaccine¿s efficacy in lowering Abeta within the nervous system and improving cognition.