** AWARDS ISSUED PRIOR TO JANUARY 20, 2025, WERE FUNDED UNDER PREVIOUS ADMINISTRATIONS AND MAY NOT REFLECT THE PRIORITIES AND POLICIES OF THE CURRENT ADMINISTRATION.** THIS STUDY IS CONDUCTED TO DEVELOP A VACCINE AGAINST SPOTTY LIVER DISEASE (SLD), WHICH IS AN IMPORTANT BACTERIAL PATHOGEN OF CHICKENS, PARTICULARLY OF COMMERCIAL LAYER HENS IN PRODUCTION STATE. TO ACHIEVE THIS GOAL, WE WILL FIRST IDENTIFY SUITABLE VACCINE CANDIDATE ANTIGENS (SMALL PEPTIDES OR MIMOTOPES) USING PHAGE DISPLAY LIBRARY AND REVERSE VACCINOLOGY STRATEGIES. NEXT, THE SELECTED MIMOTOPES WILL BE ASSESSED FOR THEIR IMMUNOGENICITY AND ABILITY TO PROTECT CHICKENS AGAINST C. HEPATICUS BY VACCINATING CHICKENS WITH E. COLI EXPRESSING THE MIMOTOPES FOLLOWED BY CHALLENGING THE VACCINATED CHICKENS WITH C. HEPATICUS. FINALLY, TO DELIVER THE MIMOTOPES IN A WAY THAT WOULD INDUCE BOTH SYSTEMIC AND MUCOSAL ANTIBODIES FOR OPTIMAL PROTECTION, THE SELECTED MIMOTOPES WILL BE CLONED INTO AN ATTENUATED STRAIN OF AVIAN PATHOGENIC E. COLI (APEC) VECTOR STRAIN. THIS APEC VECTOR STRAIN WILL BE ABLE TO CARRY MULTIPLE HETEROLOGOUS ANTIGENS AND AVAILABLE FOR MASS ADMINISTRATION VIA WATER, FOOD, OR SPRAY VACCINATION. IT IS EXPECTED THE APEC-VECTORED VACCINE CARRYING C. HEPATICUS ANTIGENS TO PROTECT CHICKENS AGAINST BOTH SLD AND E. COLI-INDUCED EGG LAYER PERITONITIS. AN EFFECTIVE VACCINE AGAINST SLD WILL AID IN THE CONTROL AND PREVENTION OF SLD, THEREBY DIMINISHING ECONOMIC LOSSES FROM MORBIDITY, MORTALITY, AND DROP IN EGG PRODUCTION ASSOCIATED WITH SLD. CONTROL OF SLD WILL BE A MAJOR BOOST TO THE COMMERCIAL EGG PRODUCTION IN THE COUNTRY. IN ADDITION TO SLD, THE FINAL E. COLI-VECTORED VACCINE IS EXPECTED TO PROTECT CHICKENS FROM ECONOMICALLY IMPORTANT APEC-INDUCED DISEASES, SUCH AS EGG PERITONITIS, THEREBY OFFERING ADDITIONAL ADVANTAGES TO THE POULTRY INDUSTRY.