Oral immunization with attenuated Salmonella enterica serovar Enteritidis expressing dual-toxin antigen induces...

Necrotizing enteritis (NE) is an important enteric disease threatening the poultry industry. Given the ban on antibiotic growth promoters, vaccination has become a safe and effective control strategy. Recombinant attenuated Salmonella vaccine (RASV) administered orally can induce comprehensive immune responses to specific antigens, thus exhibiting great prospects for inducing protective immunity against NE. In this study, a dual-toxin (PlcC and NetB) antigen expression cassette was delivered by a new attenuated Salmonella enterica serovar Enteritidis (S. Enteritidis) vector rSC0169 to construct the candidate vaccine rSC0169(pS-PGN). rSC0169(pS-PGN) effectively colonized the host lymphatic system and induced robust mucosal, humoral, and cellular immune responses to PlcC and NetB. Moreover, rSC0169(pS-PGN) alleviated intestinal lesions, improved the intestinal villus height-to-crypt depth ratio, promoted tight junction protein expression, and reduced pro-inflammatory cytokine levels. Overall, this study provides a promising NE vaccine candidate that confers protection in an experimental challenge model and lays a theoretical foundation for the development of vaccine platforms against other intestinal pathogens.