** AWARDS ISSUED PRIOR TO JANUARY 20, 2025, WERE FUNDED UNDER PREVIOUS ADMINISTRATIONS AND MAY NOT REFLECT THE PRIORITIES AND POLICIES OF THE CURRENT ADMINISTRATION.** CLASSICAL SWINE FEVER (CSF) IS A HIGHLY CONTAGIOUS VIRAL DISEASE OF PIGS THAT IS PRESENT IN SEVERAL COUNTRIES IN CENTRAL AND SOUTH AMERICA AND CAN SOON REACH THE U.S. UNLESS PREVENTATIVE MEASURES ARE TAKEN IN ENDEMIC REGIONS AND NOVEL DIAGNOSTIC METHODS FOR DETECTION ARE DEVELOPED. THE RATIONALE FOR THIS PROPOSAL IS THAT THE CURRENT CSF VACCINE USED IN COUNTRIES WITH CSF IS OUTDATED AND POSES SIGNIFICANT LIMITATIONS. IT IS A LIVE-ATTENDUATED VIRUS VACCINE, WHICH AT PRESENT CANNOT BE USED IN DISEASE-FREE COUNTRIES SUCH AS THE U.S. MOREOVER, IT FAILS TO DIFFERENTIATE BETWEEN INFECTED AND VACCINATED ANIMALS (DIVA), A CRUCIAL FEATURE OF NOVEL VACCINE CANDIDATES. THE MAJOR GOALS OF THIS PROJECT ARE TO DEVELOP (I) AN EFFICACIOUS DIVA-COMPATIBLE CSF VACCINE THAT PRODUCES RAPID AND STRONG PROTECTION AGAINST CSF DISEASE IN PIGS, AND (II) DEVELOP NOVEL DIAGNOSTIC METHODS FOR DIFFERENTIATING WILD-TYPE INFECTED ANIMALS FROM VACCINATED ANIMALS. THE TWO SPECIFIC AIMS ARE TO: (I) DEVELOP CSF VIRUS-ENVELOPE PROTEIN 2 (E2) EXPRESSING VACCINE VECTORS AND ASSESS THEM FOR IMMUNE RESPONSES AND PROTECTION AGAINST CSF DISEASE IN PIGS; AND (II) ESTABLISH DIAGNOSTIC ASSAYS THAT DIFFERENTIATE WILD-TYPE CSF-INFECTED PIGS FROM VACCINATED ANIMALS USING MODERN ANTIBODY-BASED DETECTION METHODS. BASED ON OUR PAST EXPERIENCES AND PRELIMINARY RESULTS, WE EXPECT TO DELIVER EFFICACIOUS AND SAFE CSF VACCINE CANDIDATES WHICH ARE ABLE TO PREVENT AND CONTROL CSF DISEASE IN PIGS. THIS STUDY WILL ALSO ESTABLISH A NOVEL DIAGNOSTIC METHOD FOR CSFV. THE RESULTS OF THIS RESEARCH HOLD IMMENSE POTENTIAL FOR THE SWINE INDUSTRY WORLDWIDE. BY PREVENTING THE SPREAD AND CONTROLLING THE DEVASTATING CSF DISEASE IN SWINE GLOBALLY, IT COULD POTENTIALLY SAVE BILLIONS OF DOLLARS, MAKING IT A CRUCIAL INVESTMENT FOR THE INDUSTRY.