title: An oral vaccine against NMDAR1 with efficacy in experimental stroke and epilepsy.
abstract: 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.
authors.affiliation: Department of Molecular Medicine and Department of Physiology, University of Auckland School of Medicine, Auckland, New Zealand. matthew.during@mail.tju.edu
authors.forename: M J
authors.initials: MJ
authors.lastname: During
authors.forename: C W
authors.initials: CW
authors.lastname: Symes
authors.forename: P A
authors.initials: PA
authors.lastname: Lawlor
authors.forename: J
authors.initials: J
authors.lastname: Lin
authors.forename: J
authors.initials: J
authors.lastname: Dunning
authors.forename: H L
authors.initials: HL
authors.lastname: Fitzsimons
authors.forename: D
authors.initials: D
authors.lastname: Poulsen
authors.forename: P
authors.initials: P
authors.lastname: Leone
authors.forename: R
authors.initials: R
authors.lastname: Xu
authors.forename: B L
authors.initials: BL
authors.lastname: Dicker
authors.forename: J
authors.initials: J
authors.lastname: Lipski
authors.forename: D
authors.initials: D
authors.lastname: Young
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000915:Antibody Affinity; D001323:Autoantibodies / Q000032:analysis / Q000097:blood / Q000134:cerebrospinal fluid / Q000276:immunology*; D001812:Blood-Brain Barrier; D000229:Dependovirus / Q000235:genetics; D004833:Epilepsy, Temporal Lobe / Q000473:pathology / Q000628:therapy*; D018604:Epitope Mapping; D000939:Epitopes; D005822:Genetic Vectors; D006624:Hippocampus / Q000473:pathology; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation; D009043:Motor Activity; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology*; D013226:Status Epilepticus / Q000517:prevention & control; D020521:Stroke / Q000628:therapy*; D019076:Transgenes; D014611:Vaccination; D019444:Vaccines, DNA / Q000627:therapeutic use*
chemical_list: D001323:Autoantibodies; D000939:Epitopes; D016194:Receptors, N-Methyl-D-Aspartate; D019444:Vaccines, DNA