**AWARDS ISSUED PRIOR TO JANUARY 20, 2025, WERE FUNDED UNDER PREVIOUS ADMINISTRATIONS AND MAY NOT REFLECT THE PRIORITIES AND POLICIES OF THE CURRENT ADMINISTRATION.** POST-WEANING DIARRHEA (PWD) REMAINS ONE OF THE MOST IMPORTANT PIG DISEASES, AND CUASES SUBSTANTIAL ECONOMIC LOSSES TO THE SWINE PRODUCERS. PWD AND NEONATAL DIARRHEA ARE ALSO THE MAIN REASON OF USING ANTIBIOTICS IN SWINE FARMS WHICH LINKS TO ANTIBIOTIC RESISTANCE. PWD IS CAUSED BY ENTEROTOXIGENIC ESCHERICHIA COLI (ETEC) BACTERIA PRODUCING K88 AND F18 FIMBRIAE AND ENTEROTOXINS INCLUDING HEAT-LABILE TOXIN (LT), HEAT-STABLE TOXINS (STA & STB) AND SHIGA-LIKE TOXIN STX2E. FIMBRIAE PROMOTE BACTERIA ATTACHMENT AND COLONIZATION IN PIG SMALL INTESTINES; ENTEROTOXINS DISRUPT FLUID HOMEOSTASIS IN EPITHELIAL CELLS TO CAUSE FLUID HYPER-SECRETION AND DIARRHEA. ALTHOUGH ANTIBIOTICS ADDITIVE FEEDS, ANTIBODY TREATED MEDICATION, DIETARY SUPPLEMENT, AND PROBIOTICS MAY REDUCE PWD INCIDENCE OR SEVERITY, CONCERNS ON ENVIRONMENT (AND PUBLIC HEALTH) RISKS AND COST EFFECTIVENESS LIMIT THEIR APPLICATIONS. VACCINATION IS THE MOST PRACTICAL AND EFFECTIVE, BUT NO EFFECTIVE PWD VACCINES HAVE BEEN DEVELOPED DUE TO TECHNICAL CHALLENGES AT INDUCING BROAD IMMUNITY AGAINST THE HETEROGENEOUS ETEC STRAINS. WE PROPOSE TO INNOVATIVELY PRODUCE MULTIEPITOPE FUSION ANTIGEN (MEFA) K88-F18-LT-STA-STB-STX2E AND A LIVE VACCINE INDUCING BROADLY PROTECTIVE LOCAL MUCOSAL IMMUNITY, AND TO UNAMBIGUOUSLY ASSESS EFFICACY OF THIS VACCINE IN PIGLET CHALLENGE STUDIES. WITH STRONGLY SUPPORTIVE DATA FROM PRELIMINARY STUDIES, IN CONJUGATION WITH YEARS OF COMBINED EXPERIENCE (OF TWO INVESTIGATORS) IN ETEC RESEARCH AND VACCINE DEVELOPMENT, WE BELIEVE PROPOSED RESEARCG WILL BE COMPLETED. AN EFFECTIVE PWD VACCINE WILL SAVE HUNDREDS OF MILLIONS DOLLARS EACH YEAR FOR THE US SWINE PRODUCERS AND REDUCE ANTIBIOTIC USE. ADDITIONALLY, INNOVATION APPLIED IN THIS STUDY MAY BE GENERALLY USED IN VACCINE DEVELOPMENT AGAINST OTHER DISEASES.

University Of Illinois

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