A genetically engineered vaccine against the alpha-toxin of Clostridium perfringens protects mice against experimental gas gangrene.
Fragments of the alpha-toxin of Clostridium perfringens have been produced using genetic manipulation techniques. Antibody which cross-reacted with the alpha-toxin was induced after immunization with fragments representing the N- (Cpa1-249) and C-terminal (Cpa247-370) domains of the toxin. Smaller fragments of the alpha-toxin did not induce cross-reacting antibody. Anti-Cpa1-249 serum neutralized phospholipase C activity but not haemolytic activity of the toxin. Anti-Cpa247-370 serum neutralized both the phospholipase C and haemolytic activities. Only immunization with Cpa247-370 induced protection against the lethal effects of the toxin. Immunization with Cpa247-370 also provided protection in a mouse model against at least 10 LD100 doses of C. perfringens type A. This result confirms the essential role of this toxin in the pathogenesis of gas gangrene.
Williamson
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ED
Chemical and Biological Defence Establishment, Salisbury, Wiltshire, UK.
Titball
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RW
D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000276:immunology; D000917:Antibody Formation; D001427:Bacterial Toxins / Q000037:antagonists & inhibitors / Q000633:toxicity*; D001428:Bacterial Vaccines / Q000627:therapeutic use*; D002135:Calcium-Binding Proteins; D003016:Clostridium perfringens / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D005738:Gas Gangrene / Q000517:prevention & control*; D005818:Genetic Engineering / Q000379:methods; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000276:immunology / Q000633:toxicity; D010738:Type C Phospholipases; D014614:Vaccines, Synthetic / Q000096:biosynthesis / Q000627:therapeutic use
D000906:Antibodies; D001427:Bacterial Toxins; D001428:Bacterial Vaccines; D002135:Calcium-Binding Proteins; D010446:Peptide Fragments; D014614:Vaccines, Synthetic; D010738:Type C Phospholipases; C040649:alpha toxin, Clostridium perfringens