Abstract
Poultry serve as natural reservoirs for Salmonella spp., and the consumption of Salmonella-contaminated poultry products remains a leading cause of infection in both developed and developing countries. The irrational use of antimicrobials in the poultry industry has contributed to the global emergence of multidrug-resistant (MDR) Salmonella strains. This study aimed to evaluate whether Salmonella enterica serovar Typhimurium (S. typhimurium) outer membrane vesicles (OMVs) could serve as a broad-spectrum immunogen, providing protection against the most prevalent MDR Salmonella serovars. The immunogenicity and protective efficacy of S. typhimurium OMVs were assessed in both specific-pathogen-free (SPF) mice and chickens challenged with S. typhimurium infection. In addition, the cross-protective efficacy of OMVs against infections with heterologous serovars, specifically S. montevideo and S. albany, was also evaluated in chickens. Our results demonstrated that S. typhimurium OMVs elicited a robust humoral immune response and conferred significant immune protection in both mice and chickens. Following challenges with MDR S. montevideo and S. albany strains, immunized birds exhibited reduced levels of fecal shedding and liver invasion. Furthermore, in vitro studies revealed that S. typhimurium OMVs also possess cross-immunogenicity against MDR S. Enteritidis and S. gallinarum. In conclusion, S. typhimurium OMVs provide cross-protection against heterologous MDR Salmonella infections both in vitro and in vivo. Our study suggests that OMVs derived from S. typhimurium strains hold promise as novel subunit vaccine candidates for preventing MDR heterologous serovar infections in animals, offering a potential solution to the growing challenge of antimicrobial resistance in the poultry industry.