RECOMBINANT FLAGELLIN VACCINES

PRAXIS BIOLOGICS, INC., WILL CONDUCT EXPERIMENTS TO ASSESS THE POTENTIAL OF USING BACTERIAL FLAGELLA AS CARRIERS OF FOREIGN ANTIGENIC DETERMINANTS. RECOMBINANT DNA TECHNIQUES WILL BE USED TO CONSTRUCT AND EXPRESS HYBRID FLAGELLIN MOLECULES ENCODING FOREIGN EPITOPES THAT CAN ASSEMBLE INTO FLAGELLA ON THE EXTERNAL SURFACE OF BACTERIAL CELLS. EXPERIMENTS WILL ALSO BE PERFORMED TO DETERMINE THE MAXIMUM AMOUNT OF FOREIGN DNA THAT CAN BE INSERTED INTO THE FLAGELLIN GENE, AS WELL AS THE MINIMAL FLAGELLIN SEQUENCES REQUIRED FOR ASSEMBLY INTO EXTERNAL FLAGELLAR FILAMENTS. THESE RECOMBINANT FLAGELLA WILL THEN BE ISOLATED AND PURIFIED AS PARTICULATE PREPARATIONS AND ADMINISTERED TO ANIMALS TO ASSESS IMMUNOGENICITY. IN ADDITION, LIVE, ATTENUATED SALMONELLA EXPRESSING THESE RECOMBINANT CONSTRUCTIONS WILL BE ADMINISTERED TO ANIMALS, AND THE TYPESAND MAGNITUDES OF RESPONSES WILL BE MEASURED. SUBUNIT VACCINES DESIGNED FOR IMMUNOGENICITY TO A SINGLE ANTIGEN ARE ATTRACTIVE BECAUSE OF THEIR PURITY IN RESPECT TOBOTH CONTROL OF MANUFACTURING AND THEIR LACK OF UNWANTED BIOLOGICAL SEQUELAE THAT CAN LIMIT VACCINE EFFECTIVENESS AND SAFETY. THE ABILITY TO EASILY PURIFY RECOMBINANT FLAGELLA AND ADMINISTER THEM AS PARTICULATE IMMUNOGENS, AND TO UTILIZE LIVE BACTERIA TO DELIVER THESE IMMUNOGENS ANDINDUCE A VARIETY OF IMMUNE RESPONSES, MAKE THIS TECHNOLOGY ATTRACTIVE FOR DEVELOPING AND MANUFACTURING NEW AND EFFECTIVE VACCINES.