** 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 SYNDROME VIRUS (PRRSV) HAS BEEN DAMAGING THE PORK INDUSTRY FOR OVER THREE DECADES AND IS STILL ONE OF THE MOST ECONOMICALLY SIGNIFICANT SWINE DISEASES. KILLED VACCINES ARE INEFFECTIVE; ONLY LIVE-ATTENUATED VACCINES ARE AVAILABLE, BUT THEY ARE GENERALLY CONSIDERED LESS THAN SATISFACTORY. PRRSV HAS ABILITIES TO MODULATE HOST INNATE IMMUNITY AND STIMULATE INFLAMMATORY CYTOKINE RESPONSES. PRRSV IS KNOWN TO SUPPRESS THE TYPE I IFN PRODUCTION AND DOWNSTREAM SIGNALING RESPONSIBLE FOR ANTIVIRAL PROTEIN PRODUCTION. AS A RESULT, THE DEVELOPMENT OF ADAPTIVE IMMUNE RESPONSES IS NEGATIVELY AFFECTED, AND PRRSV SURVIVES LONGER AND ESTABLISHES A PERSISTENT INFECTION IN PIGS.FURTHERMORE, PRRSV STIMULATES NF-ΚB DURING INFECTION, AND THUS PROINFLAMMATORY CYTOKINES LEVELS ARE ELEVATED, LEADING TO MORE SEVERE CLINICAL OUTCOMES (CYTOKINE STORM-LIKE), ESPECIALLY WHEN PIGS ARE COINFECTED WITH A SECONDARY BACTERIAL PATHOGEN. THE VIRAL IFN ANTAGONISM CAN BE REMOVED FROM PRRSV WITHOUT LOSING THE INFECTIVITY, AND SYNERGISTIC PRODUCTION OF INFLAMMATORY CYTOKINES CAN BE LESSENED BY REMOVING THE NF-ΚB ACTIVATION FUNCTION FROM THE VIRUS. A THIRD PROBLEM IS THE GENOME RECOMBINATION BETWEEN THE VACCINE AND THE VIRULENT VIRUS CIRCULATING IN PIG FARMS.USING THE DOUBLE-DELETION MUTANT AS THE BACKBONE VIRUS, RECOMBINATION-NEGATIVE PRRSV WILL BE GENERATED. PRRSV GENOME CONTAINS A SPECIFIC SEQUENCE ELEMENT FOR VIRAL REPLICATION, AND IT IS POSSIBLE TO REPROGRAM THE SEQUENCE ELEMENT SO THAT ANY RECOMBINATION WITH A FIELD PRRSV WILL NOT BE VIABLE IF OCCURS. THE VACCINE CANDIDATE WILL IMPROVE CLINICAL SEVERITY DURING BACTERIAL CO-INFECTION ON FARMS (ENVIRONMENTAL FACTOR), CONFER BETTER IMMUNE RESPONSES (HOST FACTOR) REGARDLESS OF THE ANTIGENIC HETEROGENEITY (VIRAL FACTORS), AND PREVENT RNA RECOMBINATION (VIRAL FACTOR) BETWEEN THE VACCINE AND VIRULENT PRRSV ON FARMS. OUR STUDY IS A NOVEL APPROACH TO DEVELOPING A FUTURE PRRSV VACCINE CANDIDATE.

University Of Illinois

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