THE GOAL OF THIS RESEARCH IS THE DEVELOPMENT OF RECOMBINANT CONTRACEPTIVE VACCINES, USING HUMAN CHORIONIC GONADOTROPIN (HCG) CARBOXY-TERMINAL PEPTIDE (CTP) AS A MODEL SYSTEM.

THE GOAL OF THIS RESEARCH IS THE DEVELOPMENT OF RECOMBINANT CONTRACEPTIVE VACCINES, USING HUMAN CHORIONIC GONADOTROPIN (HCG) CARBOXY-TERMINAL PEPTIDE (CTP) AS A MODEL SYSTEM. TO OVERCOME CURRENT CONJUGATION PROBLEMS, GENES ENCODING CON- JUGATED HCG CTP FUSED POLY-PROTEINS CAN BE SYNTHESIZED. TO OVERCOME CURRENT ADJUVANT PROBLEMS, THESE PROTEINS WILL BE DELIVERED AS A RECOMBINANT VACCINIA VACCINE. SPECIFIC AIMS OF THIS PHASE I WORK ARE: (1) CONSTRUCTING MULTIMERIC HCG CTP GENES; (2) CONSTRUCTING VECTORS THAT CREATE INTRA- CELLULAR, SECRETED, AND MEMBRANE-BOUND FORMS OF HCG CTP CONJUGATED POLYPROTEINS; (3) DETERMINING THAT THE POLY- PROTEINS ARE ANTIGENIC; AND (4) RECOMBINING THE GENES INTO VACCINIA VIRUS. PHASE II WILL INVOLVE: (1) CONSTRUCTING FURTHER RECOMBINANT VACCINIA; (2) CLONING CDNA COPIES OF THEBABOON CG (BCG) GENE TO ALLOW PROPER PRIMATE STUDIES OF VACCINE EFFICACY AND SAFETY; (3) TESTING THE ABILITY OF EACHHCG- AND BCG-VACCINIA VACCINE TO RAISE ANTISERA IN RABBITS THAT NEUTRALIZE HCG ACTIVITY IN IN VITRO AND IN VIVO RAT BIOASSAYS; AND (4) INITIATING BABOON STUDIES OF NEUTRALIZINGBCG-AND HCG-VACCINIA CONTRACEPTIVE VACCINES. THE POLY- PROTEIN TECHNOLOGY DEVELOPED WILL BE APPLICABLE TO ANY SUBUNIT OR VACCINIA VACCINE, AND THIS WORK CAN SERVE AS A MODEL FOR VACCINIA VACCINES AGAINST ANY AUTOANTIGEN.