Clostridium septicum Alpha Toxin-Based Recombinant Subunit Vaccine Protects Broiler Chickens Against Clostridial Dermatitis.

Abstract

Clostridial dermatitis (CD), caused by Clostridium septicum, is an economically important disease of broiler chickens, specifically in flocks raised without antibiotics. Our previous work in turkeys identified a nontoxic domain no. 2 of C. septicum alpha-toxin (ntATX-D2) as a protective vaccine antigen. In the present study, we used a prime-boost immunization regimen to vaccinate broiler chickens subcutaneously with recombinant ntATX-D2 protein followed by a challenge with virulent C. septicum to assess protective immunity. Immunization led to clinical protection, as determined by a significant increase in the body weight gain and a reduction in the gross and histopathological lesions in the skin, subcutis, and skeletal muscle of immunized chickens compared to the unimmunized group. Furthermore, immunological investigation of protective immunity in immunized birds when compared to the unimmunized control group revealed 1) higher levels of antigen-specific serum IgY antibodies, 2) modulation of inflammatory responses in the skin and muscle of immunized chickens, as indicated by transcriptional downregulation of proinflammatory cytokine (IL-1β, IL-6, and IFNγ) and upregulation of anti-inflammatory cytokine (IL-10 and TGFβ) genes, and 3) increased γδ T cell, B cell, and activated T-cell frequencies in the spleen and peripheral blood of immunized birds. Collectively, our findings indicated that ntATX-D2 vaccination of broiler chickens can provide protection against C. septicum-induced CD and that the mechanisms of protection seem to operate through anti-ATX antibodies coupled with modulation of local and systemic inflammatory as well as cellular immune responses.