** 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) CAUSES AN OFTEN-LETHAL DISEASE OF PIGS, BOTH WILD AND DOMESTIC THAT IS CHARACTERIZED BY A WIDE VARIETY OF CLINICAL SIGNS IN AFFECTED ANIMALS. ASFV IS A LARGE DNA VIRUS AND IS RELATIVELY VARIABLE. ALL ATTEMPTS TO DEVELOP VACCINES CAPABLE OF PROTECTING AGAINST THE INFECTION AND THE DISEASE HAVE BEEN LARGELY UNSUCCESSFUL. IN THIS PROJECT, WE WILL TEST OUR HYPOTHESIS THAT IT IS POSSIBLE TO RATIONALLY DESIGN, ENGINEER AND TEST TWO DIFFERENT VACCINE TYPES WITH RESPECT TO PROTECTION AGAINST ASFV INFECTION AND DISEASE DEVELOPMENT. OUR VACCINES WILL BE BASED ON A BETTER UNDERSTANDING OF THE PIG'S IMMUNE RESPONSE TO INFECTION AND DIFFERENT VACCINE TYPES AND VACCINATION STRATEGIES. THE TWO VACCINE TYPES TO BE TESTED ARE 1) A LIVE VIRUS VACCINES THAT IS BASED ON AN ASFV STRAIN WITH REDUCED VIRULENCE THAT WILL BE FURTHER MODIFIED BY GENOMIC ENGINEERING AND 2) VECTORED VACCINES. THE LATTER WILL CONTAIN ASFV PROTEINS THAT WILL BE DELIVERED BY TWO DIFFERENT VIRUS VECTORS, VESICULAR STOMATITIS VIRUS (VSV) AND A PARAPOXVIRUS CALLED ORF VIRUS (ORFV). DIFFERENT COMBINATIONS OF THE ENGINEERED VACCINES AND VACCINATION REGIMES WILL BE COMPARED. WE EXPECT THAT OUR APPROACH WILL RESULT IN THE INDUCTION OF ROBUST IMMUNE RESPONSES IN PIGS THAT SHOULD THEN BE PROTECTED AGAINST INFECTION AND DISEASE.