Clostridium septicum: A review in the light of alpha-toxin and development of vaccines

Clostridium septicum (CS) is a pathogen that can cause the death of animals in livestock worldwide through its main virulence factor, alpha-toxin (ATX). The aspects involved in diseases caused by ATX, such as economic impact, prevalence, and rapid clinical course, require that animals should be systematically immunized. This review provides an overview of CS in livestock farming and discusses current immunization methods. Currently, commercial vaccines available against CS involve the cultivation and inactivation of microorganisms and toxins using a time-consuming, expensive, and high biological risk-carrying production platform, and some have been reported to be ineffective. An alternative to this process is the recombinant DNA technology, although recombinant ATX obtained thus far is no longer efficient in stimulating protective antibody titers despite improvements in the production methods. On the other hand, immunized animals have highly favorable levels of survival when subjected to challenge tests, suggesting that high titers of circulating serum antibodies may not be representative of protection after immunization and that the non-immune cellular defenses associated with the particularities of the mechanism of action of ATX may be involved in the immune response of the host. To contribute to the future of global livestock farming through the development of more efficient recombinant vaccines, we suggest novel perspectives and strategies, such as the location of immunodominant epitopes, expression of relevant functional domains, and construction of chimeras, in the rational design of recombinant ATX.