Cell surface-exposed tetanus toxin fragment C produced by recombinant Bacillus anthracis protects against tetanus toxin

• Published in: Infection and Immunity Vol. 67; no. 9; pp. 4847 - 4850
• Main Authors: Mesnage, S, Weber-Levy, M, Haustant, M, Mock, M, Fouet, A
• Format: Journal Article
• Language: English
• Published: Washington, DC American Society for Microbiology 01.09.1999
• Subjects: Amino Acid Sequence; Animals; antibody formation; Bacillus anthracis; Bacillus anthracis - immunology; Bacterial Proteins; bacterial toxins; Bacterial Vaccines - immunology; Bacteriology; Biological and medical sciences; Cell Membrane - metabolism; Clostridium tetani; Fundamental and applied biological sciences. Psychology; Genetic Engineering; Membrane Glycoproteins - genetics; Membrane Glycoproteins - immunology; Mice; Microbial Immunity and Vaccines; Microbiology; Molecular Sequence Data; Peptide Fragments - genetics; Peptide Fragments - immunology; recombinant antigens; Recombinant Fusion Proteins - genetics; Tetanus Toxin - genetics; Tetanus Toxin - immunology; vaccination; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies; Vaccines, Synthetic - immunology; Recombinant microorganism; Bacillus anthracis; Cross protection; Clostridiales; Metalloendopeptidases; Bacillaceae; Bacillales; Bacteria; Tentoxilysin; Humoral immunity; Immunoprotection; Immune response; Enzyme; Antibody; Rodentia; Clostridium tetani; Vaccine; Peptidases; Toxin; Vertebrata; Mammalia; Immunogenicity; Mouse; Peptide fragment; Animal; Clostridiaceae; Hydrolases; S Layer
• ISSN: 0019-9567; 1098-5522
• DOI: 10.1128/iai.67.9.4847-4850.1999

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.