A genetically engineered vaccine against the alpha-toxin of Clostridium perfringens protects mice against experimental gas gangrene

Abstract

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.