A Noncytolytic α Toxin Recombinant Protein Protects Turkeys AgainstClostridium septicumChallenge

Clostridium septicumand its associated cytolytic α toxin, along with several other clostridial species, has been implicated as the causative agent of gangrenous dermatitis. A recombinant noncytolyticC. septicumα toxin (NCAT) peptide was developed for use as a vaccine and demonstrated to be safe at concentrations as high as 1 mg/ml. NCAT, used as a purified antigen, partially purified antigen, or in combination with native antigens, was compared to salt-fractionated α toxin combined with denaturedC. septicumbacteria (native) in a vaccination trial. Three-day-old poults were placed into one of five groups and received two, 0.2-ml vaccinations 5 wk apart. Subcutaneous challenge with 3.2 × 10⁷ log phaseC. septicumresulted in 78% to 95% of the vaccinated birds surviving challenge compared to 48% of sham-injected controls. By ELISA analysis on NCAT-coated plates, birds receiving vaccines containing the recombinant NCAT peptide showed significantly higher blood serum antibody concentrations than did birds receiving vaccines containing native antigens or alum controls. Additionally, high levels of maternally transferred antibodies reactive to NCAT-purified antigens found in the pre-immune sera from naïve 3-day-old poults suggest that the tertiary structure of the NCAT peptide has a high homology to the native protein structure. In conclusion, our study showed that the use of a vaccine comprised of a noncytolytic recombinant α toxin peptide antigen provided clinical protection equal to the use of vaccines formulated with inactivated native proteins at a reduced overall cost. Clostridium septicumy su toxina α asociada, junto con varias otras especies clostridiales, ha sido implicado como el agente causal de la dermatitis gangrenosa. Se desarrolló un péptido de una toxina α recombinante no citolítica deC. septicum(NCAT) para su uso como una vacuna y demostró ser seguro en concentraciones tan altas como 1 mg/ml. El péptido NCAT, usado como un antígeno purificado, como antígeno parcialmente purificado, o en combinación con antígenos nativos, se comparó en un ensayo de vacunación con la toxina α fraccionada con sal, combinada con bacterias desnaturalizadas deC. septicum(nativas). Se colocaron pavipollos de tres días de edad en cinco grupos y recibieron dos vacunaciones con un volumen de 0.2 ml con cinco semanas de diferencia. El desafío por vía subcutánea con 3.2 × 10⁷ deC. septicumen fase logarítmica produjo una supervivencia del 78% a 95% de las aves vacunadas y desaf