Protection Against Salmonella by Vaccination with Toxin-Antitoxin Self-Destructive Bacteria

Abstract

Salmonella is a major zoonotic foodborne pathogen. Conventional poultry vaccines, including inactivated and attenuated, may present limitations in terms of efficacy, safety and practicality. This study focuses on optimizing of a previously reported novel oral vaccination strategy employing inducible toxin-antitoxin (TA) systems, which led to self-destruction of virulent Salmonella Enteritidis both in vitro and in inoculated animals and induced a specific immune response. In a Hok/Sok (HS) TA system designed to induce cell death upon absence of arabinose, attenuation of the Hok toxin promoter, significantly prolonged bacterial survival in vitro in restrictive conditions and within macrophages. Two TA systems, Hok/Sok and CeaB/CeiB (CC), which were designed to induce cell death in low di-cation levels or anaerobic conditions, respectively, were combined to enhance vaccine safety. The combined TA system displayed complete bacterial clearance in vitro and in inoculated chickens. Immunization with the combined TA systems elicited significantly higher levels of Salmonella-specific IgY and IgA antibodies and conferred superior protection against subsequent challenge with wild-type Salmonella as compared to a commercial live vaccine. These findings highlight the potential of this adaptable TA-based vaccination platform to generate safe and efficacious Salmonella vaccines for poultry, contributing to reduced transmission in the food chain.

Keywords: Salmonella, Toxin-Antitoxin, Vaccination, Self-destructive, Hok/Sok, CeaB/CeiB.