An oral vaccine against NMDAR1 with efficacy in experimental stroke and epilepsy.
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.
During
M J
MJ
Department of Molecular Medicine and Department of Physiology, University of Auckland School of Medicine, Auckland, New Zealand. matthew.during@mail.tju.edu
Symes
C W
CW
Lawlor
P A
PA
Lin
J
J
Dunning
J
J
Fitzsimons
H L
HL
Poulsen
D
D
Leone
P
P
Xu
R
R
Dicker
B L
BL
Lipski
J
J
Young
D
D
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*
D001323:Autoantibodies; D000939:Epitopes; D016194:Receptors, N-Methyl-D-Aspartate; D019444:Vaccines, DNA