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

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

Research output: Contribution to journalArticlepeer-review

194 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1453-1460
Number of pages8
JournalScience
Volume287
Issue number5457
DOIs
StatePublished - Feb 25 2000
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • General

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