Cell surface-exposed tetanus toxin fragment C produced by recombinant Bacillus anthracis protects against tetanus toxin.
Bacillus anthracis, the causal agent of anthrax, synthesizes two surface layer (S-layer) proteins, EA1 and Sap, which account for 5 to 10% of total protein and are expressed in vivo. A recombinant B. anthracis strain was constructed by integrating into the chromosome a translational fusion harboring the DNA fragments encoding the cell wall-targeting domain of the S-layer protein EA1 and tetanus toxin fragment C (ToxC). This construct was expressed under the control of the promoter of the S-layer component gene. The hybrid protein was stably expressed on the cell surface of the bacterium. Mice were immunized with bacilli of the corresponding strain, and the hybrid protein elicited a humoral response to ToxC. This immune response was sufficient to protect mice against tetanus toxin challenge. Thus, the strategy developed in this study may make it possible to generate multivalent live veterinary vaccines, using the S-layer protein genes as a cell surface display system.
Mesnage
S
S
Toxines et Pathogénie Bactériennes, URA 1858, Centre National de la Recherche Scientifique, Institut Pasteur, Paris, France. smesnage@pasteur.fr
Weber-Levy
M
M
Haustant
M
M
Mock
M
M
Fouet
A
A
D000595:Amino Acid Sequence; D000818:Animals; D001408:Bacillus anthracis / Q000276:immunology*; D001426:Bacterial Proteins; D001428:Bacterial Vaccines / Q000276:immunology*; D002462:Cell Membrane / Q000378:metabolism; D005818:Genetic Engineering; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000235:genetics; D013744:Tetanus Toxin / Q000235:genetics / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000276:immunology*
D001426:Bacterial Proteins; D001428:Bacterial Vaccines; D008562:Membrane Glycoproteins; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; C055764:S-layer proteins; D013744:Tetanus Toxin; D014614:Vaccines, Synthetic; C040635:tetanus toxin fragment C