Print Email Facebook Twitter Instruments for oral disease-intervention strategies: Recombinant Lactobacillus casei expressing tetanus toxin fragment C for vaccination or myelin proteins for oral tolerance induction in multiple sclerosis Title Instruments for oral disease-intervention strategies: Recombinant Lactobacillus casei expressing tetanus toxin fragment C for vaccination or myelin proteins for oral tolerance induction in multiple sclerosis Author Maassen, C.B.M. Laman, J.D. Heijne den Bak-Glashouwer, M.J. Tielen, F.J. van Holten-Neelen, J.C.P.A. Hoogteijling, L. Antonissen, C. Leer, R.J. Pouwels, P.H. Boersma, W.J.A. Shaw, D.M. Publication year 1999 Abstract Lactobacillus strains possess properties that make them attractive candidates as vehicles for oral administration of therapeutics. In this report we describe the construction and analysis of recombinant Lactobacillus casei applicable in oral vaccination against an infectious disease (tetanus) and in oral tolerance induction for intervention in an autoimmune disease, multiple sclerosis. Recombinant L. casei which express surface-anchored tetanus toxin fragment C (TTFC) were generated. Quantitative analysis by flow cytometry demonstrated a high level of cell wall-bound expression of TTFC and immunogenicity was demonstrated by parenteral immunization with whole cell extracts of the recombinants. A series of expression vectors was constructed to secrete human myelin basic protein (hMBP) or hMBP as a fusion protein with β-glucuronidase from Escherichia coli. These heterologous products produced by L. casei were detected in the growth medium and parenteral immunization with this medium evoked antibodies against hMBP, confirming that secretion indeed had occurred. Based on the different localization of the heterologous proteins, lactobacilli expressing surface-anchored TTFC are ideally suited for the induction of antibody responses, whereas lactobacilli that secrete myelin proteins can be used for the induction of peripheral T-cell tolerance. In conclusion, the specific technology described here allows the construction of a wide array of safe live recombinant lactobacilli which may prove to be useful in oral intervention strategies for the prevention of infectious diseases or treatment of autoimmune diseases. Subject Experimental autoimmune/allergic encephalomyelitis (EAE)Heterologous gene expressionMucosal vaccineslactobacillus vaccineMyelin proteinRecombinant vaccineAntibody responseImmunizationImmunoblottingImmunogenicityNonhumanOral drug administrationPriority journalTetanusVaccinationAdministration, OralAnimalsBacterial VaccinesCattleFlow CytometryGenetic VectorsGuinea PigsHumansImmune ToleranceImmunohistochemistryLactobacillus caseiMiceMultiple SclerosisMyelin Basic ProteinsPeptide FragmentsRabbitsRecombinant Fusion ProteinsTetanusTetanus Toxin To reference this document use: http://resolver.tudelft.nl/uuid:5ffa237e-8515-4db5-b18b-ca16a3928593 DOI https://doi.org/10.1016/s0264-410x(99)00010-9 TNO identifier 56300 Source Vaccine, 17, 2117-2128 Document type article Files To receive the publication files, please send an e-mail request to TNO Library.