**AWARDS ISSUED PRIOR TO JANUARY 20, 2025, WERE FUNDED UNDER PREVIOUS ADMINISTRATIONS AND MAY NOT REFLECT THE PRIORITIES AND POLICIES OF THE CURRENT ADMINISTRATION.** PORCINE REPRODUCTIVE AND RESPIRATORY DISEASE SYNDROME VIRUS (PRRSV) AND PORCINE CIRCOVIRUS TYPE 3 (PCV3) ARE ECONOMICALLY IMPORTANT SWINE VIRUSES WHICH CAUSE REPRODUCTIVE FAILURE AND RESPIRATORY DISEASE. WHILE VACCINES AGAINST PCV3 ARE YET TO BE DEVELOPED, IT IS KNOWN THAT ATTENUATED VACCINES AGAINST PRRSV ARE MORE EFFECTIVE THAN INACTIVATED VACCINES. HOWEVER, ATTENUATED PRRSV VACCINES AND LIVE VACCINES IN GENERAL ARE ASSOCIATED WITH THE RISK OF REVERSION TO VIRULENCE AND RECOMBINATION WITH FIELD STRAINS. HENCE, THE PRIMARY GOAL OF THIS PROJECT IS TO DEVELOP A RAPID-ATTENUATION METHOD TARGETING ENHANCED VACCINE SAFETY WHILE RETAINING OR IMPROVING VACCINE EFFICACY. THE PROPOSED METHOD INVOLVES HARNESSING THE NATURAL PROPERTY OF RAPID MUTATION IN VIRUSES TO INDUCE SUICIDAL REPLICATION OF THE VACCINE CONSTRUCT IN THE HOST. THE PRIMARY OBJECTIVES OF THE PROJECT ARE THEREFORE TO DEVELOP DIRECTED SUICIDAL VACCINES AGAINST PRRSV AND PCV3, AND TEST THE EFFICACY AND SAFETY OF THE TEST VACCINES IN A DUAL PCV3 AND PRRSV COINFECTION MODEL. IN ADDITION, THE DATA GENERATED IS EXPECTED TO CONTRIBUTE TO THE CURRENT UNDERSTANDING PATHOGENESIS IN PCV3 AND PRRSV COINFECTIONS. THE EXPECTED PROJECT OUTPUTS INCLUDE THE DEVELOPMENT OF IMPROVED, SAFE AND EFFECTIVE VACCINES AGAINST PCV3 AND PRRSV.