The Institute for Memory Impairments and Neurological Disorders, University of California, Irvine 92697-4540, USA.
Neurobiol Dis. 2010 Sep;39(3):301-10. doi: 10.1016/j.nbd.2010.04.014. Epub 2010 May 6.
Previously we showed that anti-Abeta peptide immunotherapy significantly attenuated Alzheimer's-like amyloid deposition in the central nervous system of aged canines. In this report we have characterized the changes that occurred in the humoral immune response over 2.4years in canines immunized repeatedly with aggregated Abeta(1-42) (AN1792) formulated in alum adjuvant. We observed a rapid and robust induction of anti-Abeta antibody titers, which were associated with an anti-inflammatory T helper type 2 (Th2) response. The initial antibody response was against dominant linear epitope at the N-terminus region of the Abeta(1-42) peptide, which is identical to the one in humans and vervet monkeys. After multiple immunizations the antibody response drifted toward the elevation of antibodies that recognized conformational epitopes of assembled forms of Abeta and other types of amyloid. Our findings indicate that prolonged immunization results in distinctive temporal changes in antibody profiles, which may be important for other experimental and clinical settings.
此前我们曾表明，抗 Aβ 肽免疫疗法可显著减轻老年犬中枢神经系统中的阿尔茨海默病样淀粉样沉积。在本报告中，我们对用明矾佐剂配制的聚集 Aβ（1-42）（AN1792）反复免疫犬 2.4 年后发生的体液免疫反应变化进行了特征描述。我们观察到抗 Aβ 抗体滴度的快速和强烈诱导，这与抗炎 T 辅助型 2（Th2）反应有关。最初的抗体反应针对 Aβ（1-42）肽 N 端区域的显性线性表位，与人类和恒河猴中的表位相同。多次免疫后，抗体反应向识别 Aβ 组装形式和其他类型淀粉样蛋白构象表位的抗体升高漂移。我们的研究结果表明，长期免疫会导致抗体谱的特征性时间变化，这对于其他实验和临床环境可能很重要。
