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An epitope delivery system for use with recombinant mycobacteria

Author: Hetzel, C. · Janssen, R. · Ely, S.J. · Kristensen, N.M. · Bunting, K. · Cooper, J.B. · Lamb, J.R. · Young, D.B. · Thole, J.E.R.
Institution: TNO Preventie en Gezondheid
Source:Infection and Immunity, 8, 66, 3643-3648
Identifier: 234558
Keywords: Health · Mycobacterium antigen · Antigen expression · Immunogenicity · Mycobacterium tuberculosis · Mycobacterium vaccae · Nonhuman · Protein targeting · Vaccine production · Amino Acid Sequence · Animals · Antigens, Bacterial · Antigens, Dermatophagoides · Bacterial Proteins · CD4-Positive T-Lymphocytes · CD8-Positive T-Lymphocytes · Cloning, Molecular · Epitopes, T-Lymphocyte · Female · Gene Expression · Glycoproteins · Interferon Type II · Mice · Mice, Inbred C57BL · Molecular Sequence Data · Mycobacterium · Mycobacterium bovis · Recombinant Fusion Proteins · Recombination, Genetic · Superoxide Dismutase


We have developed a novel epitope delivery system based on the insertion of peptides within a permissive loop of a bacterial superoxide dismutase molecule. This system allowed high-level expression of heterologous peptides in two mycobacterial vaccine strains, Mycobacterium bovis bacille Calmette- Guerin (BCG) and Mycobacterium vaccae. The broader application of the system was analyzed by preparation of constructs containing peptide epitopes from a range of infectious agents and allergens. We report detailed characterization of the immunogenicity of one such construct, in which an epitope from the Der p1 house dust mite allergen was expressed in M. vaccae. The construct was able to stimulate T-cell hybridomas specific for Der p1, and it induced peptide-specific gamma interferon responses when used to immunize naive mice. This novel expression system demonstrates new possibilities for the use of mycobacteria as vaccine delivery vehicles. Chemicals/CAS: Antigens, Bacterial; Antigens, Dermatophagoides; Bacterial Proteins; Epitopes, T-Lymphocyte; Glycoproteins; Interferon Type II, 82115-62-6; Recombinant Fusion Proteins; SodA protein, Bacteria; Superoxide Dismutase, EC