A non-toxic recombinant bivalent chimeric protein rETXCSAas a potential vaccine candidate against enterotoxemia and braxy.

Abstract

Clostridium perfringens epsilon toxin (ETX) and Clostridium septicum alpha toxin (CSA) are lethal and necrotizing toxins, which play key roles in enterotoxemia and braxy of ruminants, respectively. In the present study, we synthesized a bivalent chimeric protein rETXCSAcomprising ETX(Y30A/H106P/Y196A) and CSA(C86L/N296A/H301A/W342A and a deletion of residues 212 to 222). Compared with recombinant ETX and recombinant CSA, rETXCSAshowed no cytotoxicity in Madin-Darby Canine Kidney cells and was not fatal to mice. Moreover, rETXCSAcould protect immunized mice against 10 × mouse LDof crude ETX or 3 × mouse LDof crude CSA without obvious histopathologic difference. Most importantly, both rabbits and sheep immunized with rETXCSAproduced high titers of neutralizing antibody which protected the animals against the challenge with crude ETX or crude CSA. These data suggest that genetically detoxified rETXCSAis a potential subunit vaccine candidate against enterotoxemia and braxy.