**AWARDS ISSUED PRIOR TO JANUARY 20, 2025, WERE FUNDED UNDER PREVIOUS ADMINISTRATIONS AND MAY NOT REFLECT THE PRIORITIES AND POLICIES OF THE CURRENT ADMINISTRATION.** AFRICAN SWINE FEVER VIRUS (ASFV) IS WIDESPREAD IN MANY SWINE PRODUCING COUNTRIES, CAUSING LARGE ECONOMIC LOSSES AND AFFECTING GLOBAL FOOD SECURITY. THERE ARE NO EFFECTIVE VACCINES OR TREATMENTS AVAILABLE FOR ASFV. ALTHOUGH THERE ARE STRONG EVIDENCE SUGGESTING THAT ANTIBODY IS AN IMPORTANT COMPONENT OF THE PROTECTIVE IMMUNITY, THE IDENTITY OF VIRAL PROTEINS CAPABLE OF ELICITING PROTECTIVE ANTIBODY RESPONSES IN PIGS REMAIN ELUSIVE. THIS KNOWLEDGE GAP SEVERELY HINDERS THE DEVELOPMENT OF EFFECTIVE ASFV VACCINES. IT IS OBSERVED THAT PIGS SURVIVING AN INFECTION WITH AN ASFV STRAIN OR THOSE IMMUNIZED WITH A LIVE-ATTENUATED VACCINE STRAIN DEVELOP SOLID HOMOLOGOUS PROTECTIVE IMMUNITY. ON THE OTHER HAND, PIGS VACCINATED WITH EXPERIMENTAL INACTIVATED ASF VACCINES DO NOT. WE HYPOTHESIZE THAT PIGS INFECTED WITH A LIVE ASFV STRAIN DEVELOP A DIFFERENT ANTIBODY PROFILE AS COMPARED TO THOSE VACCINATED WITH AN INACTIVATED VACCINE.THE PRIMARY GOAL OF THIS PROPOSED RESEARCH IS TO IDENTIFY VIRAL PROTEINS CAPABLE OF ELICITING A PROTECTIVE IMMUNE RESPONSE IN PIGS. IN THIS CURRENT APPLICATION, WE PROPOSE TO EMPLOY OUR RECENTLY DEVELOPED HIGH-THROUGHPUT ASSAY TO SYSTEMATICALLY SCREEN THE WHOLE ASFV PROTEOME USING ANTISERA COLLECTED FROM (1) PIGS RECOVERED FROM A NATURAL INFECTION WITH HIGHLY VIRULENT ASFV STRAIN IN THE FIELD, (2) PIGS VACCINATED WITH A LIVE-ATTENUATED ASF VACCINE AND (3) PIGS VACCINATED WITH AN INACTIVATED VACCINE. SUBSEQUENTLY, WE USED STATISTICAL TOOLS TO COMPARATIVELY ANALYZE ANTIBODY PROFILES AMONG THESE THREE POPULATIONS OF PIGS TO IDENTIFY VIRAL PROTEINS THAT HAVE THE POTENTIAL OF ELICITING PROTECTIVE ANTIBODY AGAINST ASFV.