Non-toxic perfringolysin O and α-toxin derivatives as potential vaccine candidates against bovine necrohaemorrhagic enteritis.
Bovine necrohaemorrhagic enteritis is a fatal Clostridium perfringens type A-induced disease that is characterised by sudden death. Recently the involvement of perfringolysin O and α-toxin in the development of necrohaemorrhagic lesions in the gut of calves was suggested, and thus derivatives of these toxins are potentially suitable as vaccine antigens. In the current study, the perfringolysin O derivative PFOL491D, alone or in combination with α-toxin derivative GST-cpa247-370, was evaluated as possible vaccine candidate, using in vitro assays. PFOL491Dshowed no haemolytic effect on horse red blood cells and no cytotoxic effect on bovine endothelial cells. Furthermore, calves immunised with PFOL491Draised antibodies against perfringolysin O that could inhibit the perfringolysin O-associated haemolytic activity on horse red blood cells. Antisera from calves immunised with PFOL491Dhad a significantly higher neutralising capacity against the cytotoxic effect of C. perfringens culture supernatant to bovine endothelial cells than serum from control calves (P <0.05). Immunisation of calves with PFOL491Din combination with GST-cpa247-370elicited antibodies against perfringolysin O and α-toxin and consequently inhibited both the perfringolysin O-associated haemolytic activity and the α-toxin-associated lecithinase activity in vitro. Additionally, the neutralising ability of these antisera on the cytotoxic effect of C. perfringens culture supernatant to bovine endothelial cells was significantly higher than that from calves immunised with PFOL491D(P <0.001). In conclusion, perfringolysin O derivative PFOL491Dis an immunogenic antigen that can potentially be used to produce vaccine against bovine necrohaemorrhagic enteritis. Including α-toxin derivative GST-cpa247-370has an additional protective effect and therefore vaccination of calves with a combination of both antigens seems even more promising.
Department of Pathology, Bacteriology and Avian Diseases, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, B-9820 Merelbeke, Belgium.
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Verherstraeten
Department of Pathology, Bacteriology and Avian Diseases, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, B-9820 Merelbeke, Belgium.
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Goossens
Department of Internal Medicine and Clinical Biology of Large Animals, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, B-9820 Merelbeke, Belgium.
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Valgaeren
Department of Internal Medicine and Clinical Biology of Large Animals, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, B-9820 Merelbeke, Belgium.
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Pardon
Department of Pathology, Bacteriology and Avian Diseases, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, B-9820 Merelbeke, Belgium.
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Timbermont
Department of Pathology, Bacteriology and Avian Diseases, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, B-9820 Merelbeke, Belgium.
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Haesebrouck
Department of Pathology, Bacteriology and Avian Diseases, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, B-9820 Merelbeke, Belgium.
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Ducatelle
Department of Internal Medicine and Clinical Biology of Large Animals, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, B-9820 Merelbeke, Belgium.
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Deprez
Department of Pathology, Bacteriology and Avian Diseases, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, B-9820 Merelbeke, Belgium. Electronic address: filip.vanimmerseel@ugent.be.
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Van Immerseel
D000818:Animals; D057134:Antibodies, Neutralizing / Q000187:drug effects; D001427:Bacterial Toxins / Q000276:immunology / Q000494:pharmacology*; D001428:Bacterial Vaccines / Q000276:immunology / Q000494:pharmacology; D002135:Calcium-Binding Proteins / Q000276:immunology / Q000494:pharmacology*; D002417:Cattle; D002418:Cattle Diseases / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D003015:Clostridium Infections / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control / Q000662:veterinary*; D003016:Clostridium perfringens; D042783:Endothelial Cells / Q000187:drug effects; D004751:Enteritis / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control / Q000662:veterinary*; D004912:Erythrocytes / Q000187:drug effects; D006460:Hemolysin Proteins / Q000276:immunology / Q000494:pharmacology*; D007110:Immunity, Active / Q000187:drug effects*; D010738:Type C Phospholipases / Q000276:immunology / Q000494:pharmacology*; D014614:Vaccines, Synthetic / Q000276:immunology / Q000494:pharmacology
D057134:Antibodies, Neutralizing; D001427:Bacterial Toxins; D001428:Bacterial Vaccines; D002135:Calcium-Binding Proteins; D006460:Hemolysin Proteins; D014614:Vaccines, Synthetic; C020452:Clostridium perfringens theta-toxin; D010738:Type C Phospholipases; C040649:alpha toxin, Clostridium perfringens
Calves; Clostridium perfringens; Necrohaemorrhagic enteritis; Perfringolysin O; α-toxin; θ-toxin