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Science 25 February 2000:
Vol. 287. no. 5457, pp. 1453 - 1460
DOI: 10.1126/science.287.5457.1453
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Research Articles

An Oral Vaccine Against NMDAR1 with Efficacy in Experimental Stroke and Epilepsy

Matthew J. During, 13* Charles W. Symes, 1 Patricia A. Lawlor, 1 John Lin, 2 Jane Dunning, 1 Helen L. Fitzsimons, 1 David Poulsen, 3 Paola Leone, 3 Ruian Xu, 1 Bridget L. Dicker, 1 Janusz Lipski, 2 Deborah Young 1

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.

1 Department of Molecular Medicine and
2 Department of Physiology, University of Auckland School of Medicine, Auckland, New Zealand.
3 Department of Neurosurgery, Jefferson Medical College and Thomas Jefferson University, Philadelphia, PA 19107, USA.
*   To whom correspondence should be addressed. E-mail: matthew.during{at}mail.tju.edu

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