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 expression
Mucosal vaccines
lactobacillus vaccine
Myelin protein
Recombinant vaccine
Antibody response
Immunization
Immunoblotting
Immunogenicity
Nonhuman
Oral drug administration
Priority journal
Tetanus
Vaccination
Administration, Oral
Animals
Bacterial Vaccines
Cattle
Flow Cytometry
Genetic Vectors
Guinea Pigs
Humans
Immune Tolerance
Immunohistochemistry
Lactobacillus casei
Mice
Multiple Sclerosis
Myelin Basic Proteins
Peptide Fragments
Rabbits
Recombinant Fusion Proteins
Tetanus
Tetanus Toxin
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DOI
https://doi.org/10.1016/s0264-410x(99)00010-9
TNO identifier
56300
Source
Vaccine, 17, 2117-2128
Document type
article