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**AWARDS ISSUED PRIOR TO JANUARY 20, 2025, WERE FUNDED UNDER PREVIOUS ADMINISTRATIONS AND MAY NOT REFLECT THE PRIORITIES AND POLICIES OF THE CURRENT ADMINISTRATION.** THIS FASE-EPSCOR PARTNERSHIP PROJECT WORKS ON A NOVEL PLATFORM TO IMPROVE CURRENT VACCINE CANDIDATES AGAINST PORCINE REPRODUCTIVE AND RESPIRATORY SYNDROME VIRUS (PRRSV). THE DISEASE CAUSED BY PRRSV (I.E. PRRS) IS DEVASTATING TO THE WORLD SWINE INDUSTRY AND CURRENTLY LEADS TO NEAR $800 MILLION ECONOMIC LOSS ANNUALLY IN THE US ALONE. PREVENTION OF PRRSV AND ITS ASSOCIATED DISEASES IS OF THE TOP PRIORITIES TO SWINE PRODUCERS. PRRSV QUICKLY EVOLVES THROUGH HIGH-RATE MUTATION AND SUBVERTS PORCINE ANTIVIRAL DEFENSE RESPONSES. WE HYPOTHESIZE THAT A VACCINE PLATFORM, WHICH IS CAPABLE OF EFFICIENTLY ATTENUATING FIELD STRAINS AND REVERSING THE VIRAL SUPPRESSION ON ANIMAL DEFENSE, IS KEY FOR ENHANCING EFFECTIVE IMMUNE RESPONSE RESULTING BETTER PROTECTION. OUR GOAL IS TO DEVELOP AND VALIDATE THIS VACCINE PLATFORM USING A PRRSV MODEL. USING A BIOENGINEERING APPROACH, WE HAVE MANIPULATED THE VIRAL GENOME TO CONDUCT PROOF-OF-CONCEPT STUDIES IN PIGS USING OUR VACCINE CANDIDATES. COMPARED WITH A COMMERCIAL VACCINE, WE SHOWED THAT SOME VACCINE CANDIDATES WERE MORE EFFECTIVE TO PROTECT PIGS FROM A FIELD-ISOLATE CHALLENGE WITH LOWER VIRAL LOAD AND FEVER.THIS PROJECT IS IN COLLABORATION WITH DR. LAURA MILLER AT USDA NADC AMES, IA, AND DR. BERND LEPENIES AT THE UNIVERSITY OF VETERINARY MEDICINE, HANNOVER, GERMANY. DR. MILLER WILL OVERSEE PERSONNEL AT NADC TO CONDUCT ALL PHASES OF THE ANIMAL STUDIES USING A PRRSV STRAIN UNDER BSL-2 AND A HP-PRRSV UNDER BSL3 AG CONTAINMENT AT NADC FOR THE VACCINE AND ADJUVANT STUDIES FOR OBJECTIVES. DR. LEPENIES IS A LEADER PROFESSIONAL IN C-TYPE LECTIN SIGNALING AND ADJUVANT DEVELOPMENT, AGREES TO PLAY A MENTORING ROLE AND SERVE AS AN ADVISORY CO-PI FOR THE VACCINE OPTIMIZATION.TOGETHER, WE PLAN TO FURTHER IMPROVE AND VALIDATE OUR VACCINE CANDIDATES TO ACHIEVE THE FOLLOWING SPECIFIC OBJECTIVES.(1) EXAMINE THE KINETICS OF THE IFN PEPTIDE EXPRESSION IN VIVO, AND ITS EFFECT IN POTENTIATION OF ANTIVIRAL IMMUNITY;(2) IMPLEMENT A PRRSV REVERSE-GENETIC PLATFORM TO EFFICIENTLY PRODUCE AND ATTENUATE FIELD ISOLATES AS VACCINE BACKBONES FOR IMPROVING VACCINE EFFICACY AND SAFETY; AND(3) OPTIMIZE ADJUVANT REGULATION FOR BETTER GROWTH PERFORMANCE OF VACCINATED PIGLETS.IN SUMMARY, THIS PROPOSAL WILL FURTHER VALIDATE PROMISING VACCINE CANDIDATES AND PROVIDE A REVERSE-GENETIC PLATFORM TO EFFICIENTLY GENERATE AND MODIFY VACCINES FROM FIELD ISOLATES; THEREBY, PREDICTING AN EFFECTIVE PROTECTION AGAINST EVOLVING PRRS THREATS IN THE SWINE INDUSTRY.

$640,000FY2020National Institute of Food and AgricultureUSDA

Tennessee State University, Nashville TN

Investigators

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**AWARDS ISSUED PRIOR TO JANUARY 20, 2025, WERE FUNDED UNDER PREVIOUS ADMINISTRATIONS AND MAY NOT REFLECT THE PRIORITIES AND POLICIES OF THE CURRENT ADMINISTRATION.** THIS FASE-EPSCOR PARTNERSHIP PROJECT WORKS ON A NOVEL PLATFORM TO IMPROVE CURRENT VACCINE CANDIDATES AGAINST PORCINE REPRODUCTIVE AND RESPIRATORY SYNDROME VIRUS (PRRSV). THE DISEASE CAUSED BY PRRSV (I.E. PRRS) IS DEVASTATING TO THE WORLD SWINE INDUSTRY AND CURRENTLY LEADS TO NEAR $800 MILLION ECONOMIC LOSS ANNUALLY IN THE US ALONE. PREVENTION OF PRRSV AND ITS ASSOCIATED DISEASES IS OF THE TOP PRIORITIES TO SWINE PRODUCERS. PRRSV QUICKLY EVOLVES THROUGH HIGH-RATE MUTATION AND SUBVERTS PORCINE ANTIVIRAL DEFENSE RESPONSES. WE HYPOTHESIZE THAT A VACCINE PLATFORM, WHICH IS CAPABLE OF EFFICIENTLY ATTENUATING FIELD STRAINS AND REVERSING THE VIRAL SUPPRESSION ON ANIMAL DEFENSE, IS KEY FOR ENHANCING EFFECTIVE IMMUNE RESPONSE RESULTING BETTER PROTECTION. OUR GOAL IS TO DEVELOP AND VALIDATE THIS VACCINE PLATFORM USING A PRRSV MODEL. USING A BIOENGINEERING APPROACH, WE HAVE MANIPULATED THE VIRAL GENOME TO CONDUCT PROOF-OF-CONCEPT STUDIES IN PIGS USING OUR VACCINE CANDIDATES. COMPARED WITH A COMMERCIAL VACCINE, WE SHOWED THAT SOME VACCINE CANDIDATES WERE MORE EFFECTIVE TO PROTECT PIGS FROM A FIELD-ISOLATE CHALLENGE WITH LOWER VIRAL LOAD AND FEVER.THIS PROJECT IS IN COLLABORATION WITH DR. LAURA MILLER AT USDA NADC AMES, IA, AND DR. BERND LEPENIES AT THE UNIVERSITY OF VETERINARY MEDICINE, HANNOVER, GERMANY. DR. MILLER WILL OVERSEE PERSONNEL AT NADC TO CONDUCT ALL PHASES OF THE ANIMAL STUDIES USING A PRRSV STRAIN UNDER BSL-2 AND A HP-PRRSV UNDER BSL3 AG CONTAINMENT AT NADC FOR THE VACCINE AND ADJUVANT STUDIES FOR OBJECTIVES. DR. LEPENIES IS A LEADER PROFESSIONAL IN C-TYPE LECTIN SIGNALING AND ADJUVANT DEVELOPMENT, AGREES TO PLAY A MENTORING ROLE AND SERVE AS AN ADVISORY CO-PI FOR THE VACCINE OPTIMIZATION.TOGETHER, WE PLAN TO FURTHER IMPROVE AND VALIDATE OUR VACCINE CANDIDATES TO ACHIEVE THE FOLLOWING SPECIFIC OBJECTIVES.(1) EXAMINE THE KINETICS OF THE IFN PEPTIDE EXPRESSION IN VIVO, AND ITS EFFECT IN POTENTIATION OF ANTIVIRAL IMMUNITY;(2) IMPLEMENT A PRRSV REVERSE-GENETIC PLATFORM TO EFFICIENTLY PRODUCE AND ATTENUATE FIELD ISOLATES AS VACCINE BACKBONES FOR IMPROVING VACCINE EFFICACY AND SAFETY; AND(3) OPTIMIZE ADJUVANT REGULATION FOR BETTER GROWTH PERFORMANCE OF VACCINATED PIGLETS.IN SUMMARY, THIS PROPOSAL WILL FURTHER VALIDATE PROMISING VACCINE CANDIDATES AND PROVIDE A REVERSE-GENETIC PLATFORM TO EFFICIENTLY GENERATE AND MODIFY VACCINES FROM FIELD ISOLATES; THEREBY, PREDICTING AN EFFECTIVE PROTECTION AGAINST EVOLVING PRRS THREATS IN THE SWINE INDUSTRY. · GrantIndex