Print Email Facebook Twitter Reduced experimental autoimmune encephalomyelitis after intranasal and oral administration of recombinant lactobacilli expressing myelin antigens Title Reduced experimental autoimmune encephalomyelitis after intranasal and oral administration of recombinant lactobacilli expressing myelin antigens Author TNO Preventie en Gezondheid Maassen, C.B.M. Laman, J.D. van Holten-Neelen, C. Hoogteijling, L. Groenewegen, L. Visser, L. Schellekens, M.M. Boersma, W.J.A. Claassen, E. Publication year 2003 Abstract Oral administration of autoantigens is a safe and convenient way to induce peripheral T-cell tolerance in autoimmune diseases like multiple sclerosis (MS). To increase the efficacy of oral tolerance induction and obviate the need for large-scale purification of human myelin proteins, we use genetically modified lactobacilli expressing myelin antigens. A panel of recombinant lactobacilli was constructed producing myelin proteins and peptides, including human and guinea pig myelin basic protein (MBP) and proteolipid protein peptide 139-151 (PLP139-151). In this study we examined whether these Lactobacillus recombinants are able to induce oral and intranasal tolerance in an animal model for multiple sclerosis, experimental autoimmune encephalomyelitis (EAE). Lewis rats received soluble cell extracts of Lactobacillus transformants intranasally three times prior to induction of EAE. For the induction of oral tolerance, rats were fed live transformed lactobacilli for 20 days. Ten days after the first oral administration EAE was induced. Intranasal administration of extracts containing guinea pig MBP (gpMBP) or MBP72-85 significantly inhibited EAE in Lewis rats. Extracts of control transformants did not reduce EAE. Live lactobacilli expressing guinea pig MBP72-85 fused to the marker enzyme β-glucuronidase (β-gluc) were also able to significantly reduce disease when administered orally. In conclusion, these experiments provide proof of principle that lactobacilli expressing myelin antigens reduce EAE after mucosal (intranasal and oral) administration. This novel method of mucosal tolerance induction by mucosal administration of recombinant lactobacilli expressing relevant autoantigens could find applications in autoimmune disease in general, such as multiple sclerosis, rheumatoid arthritis and uveitis. © 2003 Elsevier Ltd. All rights reserved. Chemicals/CAS: beta glucuronidase, 9001-45-0; Autoantigens; Myelin Basic Proteins Subject AutoimmunityMucosaTolerance/suppressionbeta glucuronidasecell extractguinea pig myelin basic proteinmyelin basic proteinmyelin basic protein[72-85]unclassified drugallergic encephalomyelitisanimal experimentanimal modelantigen expressionautoimmunitybacterial cellbacterium transformationcontrolled studydisease modeldrug effectfemalegene expression systemimmune systemimmunological toleranceLactobacillusmucosamultiple sclerosisnonhumanpriority journalratAdministration, IntranasalAdministration, OralAnimalsAutoantigensDisease Models, AnimalEncephalomyelitis, Autoimmune, ExperimentalEnzyme-Linked Immunosorbent AssayImmune ToleranceImmunoblottingLactobacillusMultiple SclerosisMyelin Basic ProteinsRatsRats, Inbred Lew To reference this document use: http://resolver.tudelft.nl/uuid:334b2b35-75fb-415e-80e7-1b6ec947da41 DOI https://doi.org/10.1016/s0264-410x(03)00522-x TNO identifier 237429 ISSN 0264-410X Source Vaccine, 21 (21), 4685-4693 Document type article Files To receive the publication files, please send an e-mail request to TNO Library.