** AWARDS ISSUED PRIOR TO JANUARY 20, 2025, WERE FUNDED UNDER PREVIOUS ADMINISTRATIONS AND MAY NOT REFLECT THE PRIORITIES AND POLICIES OF THE CURRENT ADMINISTRATION.** WE WILL USE SIGNIFICANTLY IMPROVED GENETICALLY DESIGNED SALMONELLA VACCINE VECTORS TO SYNTHESIZE AND DELIVER MULTIPLE PROTECTIVE ANTIGENS FROM EIMERIA MAXIMA AND E. TENELLA TO INDUCE PROTECTIVE IMMUNITY AGAINST COCCIDIOSIS IN BROILER CHICKENS. OUR CURRENT SALMONELLA VACCINE VECTORS ARE TO THE BEST OF OUR KNOWLEDGE THE MOST EXTENSIVELY GENETICALLY MODIFIED LIVING ORGANISM YET CREATED WITH GENETIC REPROGRAMMING OF SEQUENTIAL PHYSIOLOGICAL FUNCTIONS TO INDUCE PROTECTION TO PATHOGEN CHALLENGE AND THEN CULMINATING IN DEATH BY LYSIS. WE HAVE DESIGNED THESE SALMONELLA VECTORS TO ELIMINATE MEANS BY WHICH THEY (I) INHIBIT INDUCTION OF IMMUNE RESPONSES AND (II) FORMATION OF BIOFILMS THAT ENHANCE PERSISTENCE, AND WITH ADDED IMPROVED MEANS FOR (III) REGULATED DELAYED ATTENUATION, (IV) REGULATED DELAYED SYNTHESIS OF PROTECTIVE ANTIGENS AND (V) REGULATED DELAYED LYSIS IN VIVO. THE TIMING OF THESE EVENTS HAS BEEN PROGRAMMED TO MAXIMIZE THE ABILITY OF VACCINE STRAINS TO COLONIZE INTERNAL EFFECTOR LYMPHOID TISSUES AND TO PRODUCE AND DELIVER PROTECTIVE ANTIGENS PRIOR TO THE ONSET OF LYSIS, WHICH PRECLUDES PERSISTENCE IN VIVO AND VIABILITY IF SHED INTO THE ENVIRONMENT. THE REGULATED DELAYED ATTENUATION ATTRIBUTES HAVE BEEN DESIGNED TO ENHANCE THE INDUCTION OF IMMUNITY TO DIVERSE SALMONELLA SEROTYPES AS WELL AS TO OTHER MEMBERS OF THE ENTEROBACTERIACEAE. THE PROTECTIVE IMMUNITY ENHANCED SALMONELLA VACCINE (PIESV) CONSTRUCTS WILL BE EVALUATED FOR INDUCING PROTECTIVE IMMUNITY TO CHALLENGE WITH SPOROZOITES FROM E. MAXIMA AND E. TENELLA TO ELIMINATE DISEASE AND ENSURE EFFICIENT FEED CONVERSION AND MAXIMAL GROWTH ATTRIBUTES. THE VACCINE CONSTRUCTS WILL ALSO BE EVALUATED FOR THEIR ABILITY TO INDUCE PROTECTION AGAINST OTHER EIMERIA SPECIES AND IMMUNITIES TO REDUCE COLONIZATION BY VARIOUS SALMONELLA SEROTYPES FREQUENTLY COLONIZING POULTRY AND TRANSMITTED THROUGH THE FOOD CHAIN TO HUMANS. A COROLLARY OBJECTIVE IS TO REDUCE THE USE OF ANTI-MICROBIAL DRUGS IN THE REARING OF POULTRY AND THUS REDUCE PRESSURES FOR SELECTION OF DRUG-RESISTANT MICROORGANISMS.