OVER THE LAST TWO-THREE DECADES, THE SWINE INDUSTRY HAS EXPERIENCED THE EMERGENCE OF SEVERAL PATHOGENS THAT HAVE CAUSED SIGNIFICANT ECONOMIC LOSSES TO THE PORK INDUSTRY. THE MOST RECENT PATHOGEN THAT EMERGED IN SEVERAL OF THE MAJOR SWINE PRODUCING COUNTRIES WORLDWIDE IS SENECAVIRUS A, A PICORNAVIRUS, THAT CAUSES VESICULAR DISEASE IN PIGS THAT RESEMBLES FOOT-AND-MOUTH DISEASE (FMD). SINCE THE EMERGENCE OF SVA IN THE US IN THE SUMMER OF 2015, OVER 300 OUTBREAKS OF VESICULAR DISEASE HAVE BEEN CONFIRMED THROUGH LABORATORY TESTING. VESICULAR DISEASES ARE AMONG THE MOST IMPORTANT DISEASES OF LIVESTOCK. THE ANNUAL COST OF FMD, FOR EXAMPLE, HAS BEEN ESTIMATED TO AMOUNT BETWEEN $6.5 AND $21 BILLION PER YEAR IN COUNTRIES WERE THE VIRUS CIRCULATES, WHEREAS FMD OUTBREAKS IN COUNTRIES THAT ARE FREE OF THE DISEASE (LIKE THE US) COULD COST UP TO $84 BILLION. THE SIMILARITY OF SVA WITH SUCH HIGH CONSEQUENCE FADS HIGHLIGHTS THE SIGNIFICANCE OF THE DISEASE AND UNDERSCORES THE POTENTIAL IMPACT THAT THECIRCULATION OF THE VIRUS MAY HAVE IN THE US LIVESTOCK INDUSTRY. CONFUSION BETWEEN FMD WITH SVA COULD HAVE SIGNIFICANT ECONOMIC CONSEQUENCES THE US AGRICULTURE SECTOR. ALTHOUGH SOME PROGRESS HAS BEEN RECENTLY MADE AT UNDERSTANDING SVA PATHOGENESIS AND DISEASE IN PIGS, THERE ARE MANY ASPECTS OF THE VIRUS AND THE MECHANISMS THAT LEAD TO DISEASE THAT ARE STILL UNKNOWN. ADDITIONALLY, CURRENTLY THERE ARE NO VACCINES AVAILABLE TO PREVENT THE DISEASE IN PIGS.THE PRESENT STUDY ADDRESSES THESE ISSUES AND IS AIMED AT IMPROVING OUR UNDERSTANDING OF THE MECHANISMS THAT SVA USES TO CAUSE DISEASE IN PIGS (OBJECTIVE 1) WITH THE ULTIMATE GOAL OF USING THIS KNOWLEDGE TO DEVELOP VACCINE CANDIDATES TO PREVENT AND CONTROL THE DISEASE IN THE FIELD (OBJECTIVE 2). TO ACHIEVE THESE OBJECTIVES WE WILL EMPLOY MOLECULAR VIROLOGY TECHNIQUES TO MANIPULATE THE GENOME OF SVA AND IDENTIFY GENETIC SIGNATURES THAT CONTRIBUTE TO THE VIRUS PATHOGENICITY AND THAT ARE REQUIRED FOR THE DEVELOPMENT OF VESICULAR DISEASE IN PIGS. ONCE THESE GENETIC SIGNATURES HAVE BEEN IDENTIFIED IN OBJETIVE 1, WE WILL USE THIS KNOWLEDGE TO DEVELOP LIVE ATTENUATED VACCINE CANDIDATES FOR SVA. THE SAFETY AND EFFICACY OF THE VACCINE CANDIDATES WILL BE EVALUATED IN PIGS AGAINST CHALLENGE INFECTION WITH FIELD STRAINS OF SVA. THE OBJECTIVES OF THIS STUDY ARE RELATED TO THE USDA PROGRAM AREA OF ANIMAL HEALTH AND DISEASE (PRIORITY CODE A1221). SUCCESSFUL COMPLETION OF THIS PROJECT WILL SIGNIFICANTLY IMPACT THE PRIORITY AREAS OF ANIMAL PRODUCTS - ANIMAL SYSTEMS AND THE SUB PRIORITY AREA OF DISEASE PREVENTION BY IMPROVING OUR UNDERSTANDING OF THE MECHANISMS UNDERLYING THE SVA DISEASE PROCESS AND BY FOCUSING ON THE DEVELOPMENT OF VACCINES FOR USE IN SWINE.