During M J, Symes C W, Lawlor P A, Lin J, Dunning J, Fitzsimons H L, Poulsen D, Leone P, Xu R, Dicker B L, Lipski J, Young D
Department of Molecular Medicine and Department of Physiology, University of Auckland School of Medicine, Auckland, New Zealand.
Science. 2000 Feb 25;287(5457):1453-60. doi: 10.1126/science.287.5457.1453.
The brain is generally considered immunoprivileged, although increasing examples of immunological responses to brain antigens, neuronal expression of major histocompatibility class I genes, and neurological autoimmunity have been recognized. An adeno-associated virus (AAV) vaccine generated autoantibodies that targeted a specific brain protein, the NR1 subunit of the N-methyl-D-aspartate (NMDA) receptor. After peroral administration of the AAV vaccine, transgene expression persisted for at least 5 months and was associated with a robust humoral response in the absence of a significant cell-mediated response. This single-dose vaccine was associated with strong anti-epileptic and neuroprotective activity in rats for both a kainate-induced seizure model and also a middle cerebral artery occlusion stroke model at 1 to 5 months following vaccination. Thus, a vaccination strategy targeting brain proteins is feasible and may have therapeutic potential for neurological disorders.
尽管对脑抗原的免疫反应、主要组织相容性复合体I类基因的神经元表达以及神经自身免疫的实例越来越多，但大脑通常被认为具有免疫豁免权。一种腺相关病毒（AAV）疫苗产生了靶向一种特定脑蛋白（N-甲基-D-天冬氨酸（NMDA）受体的NR1亚基）的自身抗体。经口给予AAV疫苗后，转基因表达持续至少5个月，并且在没有显著细胞介导反应的情况下与强烈的体液反应相关。这种单剂量疫苗在接种后1至5个月对大鼠的海藻酸诱导癫痫模型和大脑中动脉闭塞性中风模型均具有强大的抗癫痫和神经保护活性。因此，针对脑蛋白的疫苗接种策略是可行的，并且可能对神经系统疾病具有治疗潜力。
