WE ORIGINALLY DEVELOPED SELF-DESTRUCTING ATTENUATED ADJUVANT SALMONELLA (SDAAS) STRAINS TO DELIVER PATHOGEN-ASSOCIATED MOLECULAR PATTERNS (PAMPS) AND DAMAGE-ASSOCIATED MOLECULAR PATTERNS (DAMPS) TO PATTERN RECOGNITION RECEPTORS (PRRS) TO AUGMENT ABILITY OF SUBUNIT AND LIVE VACCINES TO INDUCE PROTECTIVE IMMUNITY. THESE LIVE STRAINS EFFICIENTLY COLONIZE MUCOSAL SURFACES AND INVADE LYMPHOID TISSUES TO ACTIVATE INNATE IMMUNITY EFFECTORS. WE THEN DEMONSTRATED THAT SDAAS STRAINS WERE SAFE AND EFFICACIOUS FOR IN OVO ADMINISTRATION TO 18-DAY-OLD CHICKEN EMBRYOS TO ACHIEVE NORMAL HATCHABILITY. CHICKS HATCHED FROM THESE IN OVO INOCULATED EMBRYOS DISPLAY INCREASED PROTECTION AGAIN COLONIZATION BY S. TYPHIMURIUM. WE THEREFORE PROPOSE TO FURTHER OPTIMIZE SDAAS STRAINS FOR DELIVERY BY COMMERCIAL MEANS USED IN HATCHERIES AND EVALUATE THEIR ABILITY AFTER IN OVO ADMINISTRATION TO REDUCE NATURAL MEANS OF COLONIZATION BY SALMONELLA, CAMPYLOBACTER JEJUNI, CLOSTRIDIUM PERFRINGENS AND APEC STRAINS. WE WILL ALSO INVESTIGATE ALREADY CONSTRUCTED PROTECTIVE IMMUNITY ENHANCED SALMONELLA VACCINE (PIESV) CONSTRUCTS (AND ONE TO BE MADE AGAINST APEC STRAINS) TO BE CO-ADMINISTERED WITH SDAAS STRAINS BY IN OVO INOCULATION OR BY COURSE SPRAY AT DAY-OF-HATCH TO AUGMENT LEVELS OF PROTECTIVE IMMUNITY TO THESE PATHOGENS. OUR ULTIMATE GOAL IS TO ENSURE SAFE EFFICACIOUS IN OVO INOCULATION TO STIMULATE PRODUCTION OF SUSTAINED INNATE IMMUNITY AND CONFER IMPROVED PROTECTIVE IMMUNITY AGAINST SALMONELLA, C. JEJUNI, C. PERFRINGENS AND APEC INFECTIONS AND DISEASE. SUCCESS WILL LEAD TO HEALTHIER CHICKENS, WITH IMPROVED FEED CONVERSION AND INCREASED WEIGHT GAIN, REDUCED USE OF ANTIMICROBIAL DRUGS MINIMIZING SELECTIVE PRESSURE FOR EXPANSION IN DRUG-RESISTANT BACTERIA AND REDUCE PASSAGE OF ENTERIC PATHOGENS THROUGH THE FOOD CHAIN TO HUMANS