Cross-protective Salmonella vaccine reduces cecal and splenic colonization of multidrug-resistant Salmonella enterica serovar Heidelberg

•Salmonella vaccine BBS 866 is avirulent in turkeys.•Vaccination reduces cecal colonization by outbreak-associated MDR S. Heidelberg.•Vaccination limits systemic dissemination of S. Heidelberg to the turkey spleen.•BBS 866 cross-protects diverse animal species against different Salmonella serovars. Salmonella vaccine strategies for food-producing animals have typically focused on a specific serovar that either causes production losses due to morbidity/mortality or is an important food safety pathogen for a particular food commodity. The Salmonella enterica serovar Typhimurium BBS 866 vaccine strain was designed to reduce serovar specificity to provide cross-protection against diverse Salmonella serovars, thereby broadening its applicability for multiple animal and poultry species. We reported cross-protection of the BBS 866 vaccine in swine [Vaccine 34:1241–6]. In the current study, we extend the efficacy of the Salmonella vaccine to a poultry commodity by revealing significant reduction of multidrug-resistant Salmonella enterica serovar Heidelberg colonization of the cecum and systemic dissemination to the spleen in BBS 866-vaccinated turkeys. Transcriptional analysis of whole blood from BBS 866-vaccinated turkeys revealed down-regulation of metabolic and immune genes (KCNAB1, ACOD1, GPR17, ADOR2AB, and IL-17RD), suggesting limited leukocyte activation without an overt peripheral inflammatory response to vaccination.