SYNTHETIC VACCINES UTILIZING BACULOVIRUS POLYHEDRA

THE AIM OF THIS PROPOSAL IS THE ADAPTATION OF BACULOVIRUS FOR THE PRODUCTION OF SYNTHETIC VACCINES. LATE AFTER INFECTION, BACULOVIRUS-INFECTED CELLS PRODUCE PARACRYSTALLINE OCCLUSION BODIES THAT CONSIST PRIMARILY OF ASINGLE PROTEIN, POLYHEDRIN. AMERICAN BIOGENETIC SCIENCES, INC. INTENDS TO MODIFY THE POLYHEDRIN GENE OF AUTOGRAPHA CALIFORNICA TO GENERATE RECOMBINANT OCCULSION BODIES EXPOSING ANTIGENIC DETERMINANTSOF PATHOGENIC MICROORGANISMS. THIS REQUIRES (1) IDENTIFYINGTHE APPROPRIATE REGIONS OF THE POLYHEDRIN IN WHICH TO INSERT SEQUENCES ENCODING NEW ANTIGENIC DETERMINANTS, (2) CONSTRUCTING RECOMBINANT POLYHEDRIN GENES IN VITRO, (3) TRANSFERRING THE RECOMBINANT GENES INTO THE BACULOVIRUS GENOME, (4) EXPRESSING THE HYBRID GENE AND GENERATING RECOMBINANT OCCLUSION BODIES, AND (5) CHARACTERIZING NEW EPITOPES EXPRESSED ON THE RECOMBINANT CRYSTAL. ANTIGENIC DETERMINANTS OF WELL-CHARACTERIZED PROTEINS WILL BE USED TO DEMONSTRATE THE FEASIBILITY OF THE TECHNIQUE. LATER, ANTIGENIC DETERMINANTS OF PATHOGENS WILL BE EXPRESSED. THE SYSTEM OFFERS SEVERAL POTENTIAL ADVANTAGES, INCLUDING THE HIGH LEVEL OF EXPRESSION OF THE BACULOVIRUS EXPRESSION SYSTEM, THE EASE OF PURIFICATION OF OCCLUSION BODIES, AND THEIR PRODUCTION IN A SYSTEM FREE OF HUMAN PATHOGENS. IN ADDITION, THE OCCLUSION BODIES ARE LARGE STRUCTURES; THIS SHOULD ENHANCE THE IMMUNOGENICITY OF THE EXPOSED EPITOPES AND PERMIT THE PRESENTATION OF MANY COPIES OF THE ANTIGENIC DETERMINANT.