Salmonella-vectored vaccine delivering three Clostridium perfringens antigens protects poultry against necrotic enteritis

Abstract

Necrotic enteritis is an economically important poultry disease caused by the bacterium Clostridium perfringens . There are currently no necrotic enteritis vaccines commercially available for use in broiler birds, the most important target population. Salmonella -vectored vaccines represent a convenient and effective option for controlling this disease. We used a single attenuated Salmonella vaccine strain, engineered to lyse within the host, to deliver up to three C . perfringens antigens. Two of the antigens were toxoids, based on C . perfringens α-toxin and NetB toxin. The third antigen was fructose-1,6-bisphosphate aldolase (Fba), a metabolic enzyme with an unknown role in virulence. Oral immunization with a single Salmonella vaccine strain producing either Fba, α-toxoid and NetB toxoid, or all three antigens, was immunogenic, inducing serum, cellular and mucosal responses against Salmonella and the vectored C . perfringens antigens. All three vaccine strains were partially protective against virulent C . perfringens challenge. The strains delivering Fba only or all three antigens provided the best protection. We also demonstrate that both toxins and Fba are present on the C . perfringens cell surface. The presence of Fba on the cell surface suggests that Fba may function as an adhesin.

Sodium Butyrate Reduces Salmonella Enteritidis Infection of Chicken Enterocytes and Expression of Inflammatory Host Genes in vitro

“…Different approaches have been investigated to reduce SE colonization in chickens which include feeding competitive exclusion bacteria ( Stern et al, 2001 ; Revolledo et al, 2006 ; Kim et al, 2020 ) antibiotics ( Chadfield and Hinton, 2004 ), bacteriophages ( Fiorentin et al, 2005 ; Atterbury et al, 2007 ; Nabil et al, 2018 ), vaccines ( Inoue et al, 2008 ; Bearson et al, 2019 ; Wilde et al, 2019 ), plant derived compounds ( Kollanoor-Johny et al, 2012 ; Upadhyaya et al, 2013 , 2015 ; Darre et al, 2014 ; Johny et al, 2017 ), and organic acids ( Xiong et al, 2016 ; Wu et al, 2018 ). However, limited antimicrobial efficacy, toxicity, palatability concerns, or adverse effect on production parameters necessitates the exploration of new antimicrobial compound for controlling Salmonella colonization in chickens.…”

Multifunctional Fructose 1,6-Bisphosphate Aldolase as a Therapeutic Target

“…Both Mycoplasma bovis and Mycoplasma hyopneumoniae , devastating pathogenic agents of bovine bronchopneumonia ( M. bovis ) and porcine enzootic pneumonia ( M. hyopneumoniae ) possess surface-exposed aldolase as revealed by immunofluorescence ( Gao et al, 2018 ), and flow cytometry of live bacterial cells stained with an anti-FBA antibody ( Yu et al, 2018 ), respectively. Immunofluorescence assays confirmed the presence of aldolase on the surface of Clostridium perfringens , a causative agent of necrotic enteritis in poultry ( Wilde et al, 2019 ). Cell fractionation and western blot analysis also revealed the presence of aldolase on the surface of the bacterial pathogen Klebsiella pneumoniae, a causative agent of disseminated K. pneumoniae invasive syndrome–a complication for some diabetics ( Lee et al, 2020 ).…”

An atypical lipoteichoic acid from Clostridium perfringens elicits a broadly cross-reactive and protective immune response

“…The discovery that the major antigen recognized by this immune response was a nonproteinaceous antigen suggests that although vaccines targeting C. perfringens toxins may reduce the risk or severity of disease, these and other vaccines targeting protein antigens are unlikely to induce killing or clearing of C. perfringens cells from the intestinal tract. This may explain why several toxoid vaccines and one pilin-based vaccine show reduction in C. perfringens-induced lesion scores in chickens but are unable to fully eliminate lesions in at least half of vaccinated birds (30,(41)(42)(43).…”