CAMPYLOBACTER AND SALMONELLA ARE LEADING FOOD PATHOGENS WORLDWIDE AND MAJOR PUBLIC HEALTH PROBLEMS. AMONG 31 MAJOR PATHOGENS, THEY CAUSE 20% OF ILLNESSES, 50% OF HOSPITALIZATIONS, AND 28% OF DEATHS IN 9.4 MILLION EPISODES OF FOODBORNE ILLNESSES. BLOCKING TRANSMISSION OF THESE TWO PATHOGENS THROUGH THE FOOD CHAIN TO HUMANS IS A HIGH PRIORITY. WE WILL USE NEW INNOVATIVE TECHNOLOGIES TO CONSTRUCT RECOMBINANT ATTENUATED SALMONELLA VACCINES (RASVS) TO IDENTIFY AND DELIVER BY COURSE SPRAY/ORAL IMMUNIZATION MULTIPLE C. JEJUNI PROTECTIVE ANTIGENS TO PREVENT INFECTION AND PERSISTENCE OF CAMPYLOBACTER IN CHICKENS. SINCE S. ENTERITIDIS IS THE MOST TRANSMISSIBLE SALMONELLA SEROTYPE VIA EGGS AND CAUSES THE MOST SEVERE DISEASE WHEN TRANSMITTED TO HUMANS, WE WILL DEVELOP A HYBRID VACCINE TO PRESENT S. ENTERITIDIS-SPECIFIC ANTIGENS, INDUCE CROSS-PROTECTIVE IMMUNITY TO OTHER SALMONELLA SEROTYPES AND DELIVER MULTIPLE C. JEJUNI PROTEIN ANTIGENS. A SECOND RASV DERIVED FROM OUR BEST S. TYPHIMURIUM VACCINEWILL BE ENGINEERED TO DISPLAY THE C. JEJUNI-SPECIFIC PROTECTIVE N-GLYCAN. USE OF THESE RASVS TOGETHER WILL REDUCE TRANSMISSION OF BOTH SALMONELLA AND C. JEJUNI THROUGH THE FOOD CHAIN TO HUMANS. WE WILL APPLY 30 YEARS OF ACCUMULATED EXPERTISE IN THE GENETIC MODIFICATION OF SALMONELLA AND IN THE DESIGN, CONSTRUCTION AND EVALUATION OF RASVS TO IDENTIFY/CONFIRM CONSERVED PROTECTIVE CAMPYLOBACTER ANTIGENS. OUR RASVS WILL EXHIBIT A REGULATED LYSIS IN VIVO PHENOTYPE THAT INDUCES THE MOST SUPERIOR LEVELS OF PROTECTIVE IMMUNITY AGAINST SEVERAL POULTRY PATHOGENS COMPARED TO RASVS WITHOUT THIS LYSIS PHENOTYPE. THESE RASVS ALSO EXHIBIT COMPLETE BIOLOGICAL CONTAINMENT WITH NO PERSISTENCE IN VIVO AND NO SURVIVAL IF EXCRETED.