An oral vaccine against NMDAR1 with efficacy in experimental stroke and epilepsy

The brain is generally considered immunoprivileged, although increasing exa mples 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 autoanti bodies that targeted a specific brain protein, the NR1 subunit of the N-met hyl-D-aspartate (NMDA) receptor. After peroral administration of the AAV va ccine, transgene expression persisted for at least 5 months and was associa ted with a robust humoral response in the absence of a significant cell-med iated response. This single-dose vaccine was associated with strong anti-ep ileptic and neuroprotective activity in rats for both a kainate-induced sei zure model and also a middle cerebral artery occlusion stroke model at 1 to 5 months following vaccination. Thus, a vaccination strategy targeting bra in proteins is feasible and may have therapeutic potential for neurological disorders.