** AWARDS ISSUED PRIOR TO JANUARY 20, 2025, WERE FUNDED UNDER PREVIOUS ADMINISTRATIONS AND MAY NOT REFLECT THE PRIORITIES AND POLICIES OF THE CURRENT ADMINISTRATION.** THE CAPACITY OF SALMONELLA TO SUCCESSFULLY COLONIZE AND TRANSMIT IN CHICKENS IS THE MOST CRITICAL FEATURE CONTRIBUTING TO PUBLIC FOOD SAFETY CONCERNS DUE TO CONSUMPTION OF SALMONELLA-CONTAMINATED CHICKEN MEAT. ALTHOUGH A GREAT DEAL OF EFFORT HAS BEEN MADE TOWARD UNDERSTANDING GUT COLONIZATION BY SALMONELLA, THE MECHANISMS UNDERLYING HORIZONTAL TRANSMISSION REMAIN LARGELY UNKNOWN. IN THIS PROJECT, WE WILL DEVELOP A NOVEL VACCINATION STRATEGY TO CONTROL SALMONELLA IN CHICKENS BASED ON THE TWO KEY CONCEPTS RECENTLY DEVELOPED BY OUR TEAM. IN OBJECTIVE 1, WE WILL OPTIMIZE AND EVALUATE THE USE OF DNA-BASED APTAMER ADJUVANT TARGETING CD40 AS A UNIVERSAL BIVALENT SYSTEM. IN OBJECTIVE 2, WE WILL USE A POWERFUL FUNCTIONAL GENOMICS TOOL, TRANSPOSON SEQUENCING, TO IDENTIFY GENETIC FACTORS IN SALMONELLA TYPHIMURIUM REQUIRED FOR HORIZONTAL TRANSMISSION. IN OBJECTIVE 3, THE NOVEL VACCINATION STRATEGY DEVELOPED IN OBJECTIVE 1 WILL BE ADOPTED TO TARGET THE TRANSMISSION FACTORS IDENTIFIED IN OBJECTIVE 2 TO REDUCE HORIZONTAL TRANSMISSION IN A CHICKEN FLOCK. THE RESULTS OF THIS PROJECT WILL PROVIDE PREVIOUSLY UNKNOWN MECHANISTIC INSIGHTS ON SALMONELLA HORIZONTAL TRANSMISSION AND A VERSATILE AND UNIVERSAL VACCINATION PLATFORM THAT CAN BE USED FOR EFFECTIVE CONTROL OF THE HORIZONTAL TRANSMISSION AND THUS THE PREVALENCE OF SALMONELLA IN A CHICKEN FLOCK.