INFLUENZA A VIRUSES (IAV) CAUSE SIGINIFIANCT ECOMONIC LOSS IN LIVESTOCK INDUSTRY. THE ZOONOTIC NATURE OF THE VIRUS ALSO POSE A SIGNIFICANT PANDEMIC THREAT TO HUMAN POPULATION. PIGS HAVE LONG BEEN CONSIDERED A MIXING VESSEL FOR GENERATION OF NOVEL INFLUENZA VIRUSES. THE RECENT EMERGENCE AND OUTBREAKS OF HIGHLY PATHOGENIC AVIAN INFLUENZA (HPAI) H5N1 VIRUS IN CATTLE HAVE INCREASED CONCERN OF IAV PANZOOTIC/PANDEMIC IN ANIMALS AND HUMAN POPULATION. AN UNIVERSAL VACCINE THAT CAN INDUCE STRONG, BROADLY PROTECTIVE IMMUNITY AGAINST GENETICALLY DIVERSIFIED VIRAL STRAINS IS URGENTLY NEEDED. CURRENT COMMERCIAL INFLUENZA VACCINE PLATFORMS AND MANUFACTURING PROCEDURES PRESENT A CHALLENGE FOR US TO RESPOND TO AN INFLUENZA OUTBREAK IN A TIMELY MANNER. NUCLEIC ACID-BASED (MRNA) VACCINE PLATFORMS ALLOW FOR FLEXIBLE, NIMBLE, LARGE-SCALE PRODUCTION OF VACCINES, WHICH CAN MEET THE RAPID MANUFACTURING REQUIREMENTS DURING AN INFLUENZA OUTBREAK. IN THIS PROPOSED STUDY, WE WILL TEST AN MRNA VACCINE COCKTAIL, WHICH CONTAINS A MIXTURE OF MRNAS ENCODING A CHIMERIC HA (H1) GLOBULAR HEAD, WITH TWO TYPES OF CONSERVED HA STALK DOMAIN COVERING 16 IAV SUBTYPES, AND THE H5 ANTIGEN FROM HPAI H5N1. THESE MRNAS WILL BE DELIVERED BY A NOVEL CLASS OF PEPTIDE-BASED CATIONIC NANOPARTICLES (PNP) FEATURING RESISTANCE TO OXIDATION AND THERMAL STABILITY. THIS CANDIDATE MRNA-PNP VACCINE WILL BE INITIALLY CHARACTERIZED IN CELL CULTURE MODEL AND THE IMMUNOGENICITY OF VACCINE WILL BE ASSESSED IN ANIMAL MODELS, INCLUDING PIGS AND CALVES.