The C-terminal domain of Clostridium perfringens alpha toxin as a vaccine candidate against bovine necrohemorrhagic enteritis.

Evy Goossens,Leen Timbermont,Bonnie R Valgaeren,Piet R Deprez,Diego Rodrigo-Mocholí,Stijn Schauvliege,Richard Ducatelle,Bart Pardon,Freddy Haesebrouck,Filip Van Immerseel,Stefanie Verherstraeten

doi:10.1186/s13567-016-0336-y

Abstract

Bovine necrohemorrhagic enteritis is caused by Clostridium perfringens and leads to sudden death. Alpha toxin, together with perfringolysin O, has been identified as the principal toxin involved in the pathogenesis. We assessed the potential of alpha toxin as a vaccine antigen. Using an intestinal loop model in calves, we investigated the protection afforded by antisera raised against native alpha toxin or its non-toxic C-terminal fragment against C. perfringens-induced intestinal necrosis. Immunization of calves with either of the vaccine preparations induced a strong antibody response. The resulting antisera were able to neutralize the alpha toxin activity and the C. perfringens-induced endothelial cytotoxicity in vitro. The antisera raised against the native toxin had a stronger neutralizing activity than those against the C-terminal fragment. However, antibodies against alpha toxin alone were not sufficient to completely neutralize the C. perfringens-induced necrosis in the intestinal loop model. The development of a multivalent vaccine combining the C-terminal fragment of alpha toxin with other C. perfringens virulence factors might be necessary for complete protection against bovine necrohemorrhagic enteritis.

Highlights

Clostridium perfringens is a Gram-positive, spore-forming, anaerobic bacterium
We recently showed that vaccination of calves with a mixture of native toxins from C. perfringens induces antibodies that protect against C. perfringens challenge in an intestinal loop model of bovine necrohemorrhagic enteritis (Goossens et al, provisionally accepted)
Alpha toxin is involved in the induction of necrotic lesions in a calf intestinal loop model and is an important toxin in the pathogenesis of enterotoxaemia

Summary

Introduction

Clostridium perfringens is a Gram-positive, spore-forming, anaerobic bacterium. It is a normal component of the intestinal microbiota of animals, including humans. It secretes several toxins and enzymes that cause different forms of tissue damage [1,2,3]. It can cause a variety of diseases in various vertebrates [2]. Alpha toxin and perfringolysin O have been identified as the principal toxins involved in gas gangrene caused by C. perfringens as well as in bovine necrohemorrhagic enteritis [4]. Gas gangrene is a frequently lethal histotoxic infection of humans and animals characterized by rapid

Objectives

Methods

Results

Conclusion