An epitope delivery system for use with recombinant mycobacteria.
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-Guérin (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.
Hetzel
C
C
Department of Biology, Imperial College School of Medicine, London, United Kingdom.
Janssen
R
R
Ely
S J
SJ
Kristensen
N M
NM
Bunting
K
K
Cooper
J B
JB
Lamb
J R
JR
Young
D B
DB
Thole
J E
JE
D000595:Amino Acid Sequence; D000818:Animals; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology*; D039741:Antigens, Dermatophagoides; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003001:Cloning, Molecular; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D015870:Gene Expression; D006023:Glycoproteins / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009161:Mycobacterium / Q000235:genetics / Q000276:immunology*; D009163:Mycobacterium bovis / Q000235:genetics / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D011995:Recombination, Genetic; D013482:Superoxide Dismutase / Q000235:genetics / Q000276:immunology*
D000942:Antigens, Bacterial; D039741:Antigens, Dermatophagoides; D001426:Bacterial Proteins; D018984:Epitopes, T-Lymphocyte; D006023:Glycoproteins; D011993:Recombinant Fusion Proteins; D007371:Interferon-gamma; C095500:SodA protein, Bacteria; D013482:Superoxide Dismutase