Cross-Protective Efficacy of Outer Membrane Vesicles (OMVs) Derived from Salmonella enterica Serovar Typhimurium Against Salmonella enterica Serovars Colonization in SPF Chicken

Poultry serve as natural reservoirs for <i>Salmonella</i> spp., and the consumption of <i>Salmonella</i>-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) <i>Salmonella</i> strains. This study aimed to evaluate whether <i>Salmonella enterica</i> serovar Typhimurium (<i>S. typhimurium</i>) outer membrane vesicles (OMVs) could serve as a broad-spectrum immunogen, providing protection against the most prevalent MDR <i>Salmonella</i> serovars. The immunogenicity and protective efficacy of <i>S. typhimurium</i> OMVs were assessed in both specific-pathogen-free (SPF) mice and chickens challenged with <i>S. typhimurium</i> infection. In addition, the cross-protective efficacy of OMVs against infections with heterologous serovars, specifically <i>S. montevideo</i> and <i>S. albany,</i> was also evaluated in chickens. Our results demonstrated that <i>S. typhimurium</i> OMVs elicited a robust humoral immune response and conferred significant immune protection in both mice and chickens. Following challenges with MDR <i>S. montevideo</i> and <i>S. albany</i> strains, immunized birds exhibited reduced levels of fecal shedding and liver invasion. Furthermore, in vitro studies revealed that <i>S. typhimurium</i> OMVs also possess cross-immunogenicity against MDR S. Enteritidis and <i>S. gallinarum</i>. In conclusion, <i>S. typhimurium</i> OMVs provide cross-protection against heterologous MDR <i>Salmonella</i> infections both in vitro and in vivo. Our study suggests that OMVs derived from <i>S. typhimurium</i> 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.