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
Autoimmunity
Mucosa
Tolerance/suppression
beta glucuronidase
cell extract
guinea pig myelin basic protein
myelin basic protein
myelin basic protein[72-85]
unclassified drug
allergic encephalomyelitis
animal experiment
animal model
antigen expression
autoimmunity
bacterial cell
bacterium transformation
controlled study
disease model
drug effect
female
gene expression system
immune system
immunological tolerance
Lactobacillus
mucosa
multiple sclerosis
nonhuman
priority journal
rat
Administration, Intranasal
Administration, Oral
Animals
Autoantigens
Disease Models, Animal
Encephalomyelitis, Autoimmune, Experimental
Enzyme-Linked Immunosorbent Assay
Immune Tolerance
Immunoblotting
Lactobacillus
Multiple Sclerosis
Myelin Basic Proteins
Rats
Rats, 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