The goal of this research is the development of improved human chorionic gonadotropin (hCG) carboxy-terminal peptide (CTP) contraceptive vaccines. To overcome current conjugation problems, genes encoding """"""""conjugated"""""""" hCG CTP fused polyproteins will be synthesized. To overcome current adjuvant problems, these proteins will be delivered as a recombinant hCG-vaccinia vaccine. Phase I specific aims are: 1) constructing multimeric hCG CTP genes; 2) constructing vectors that create intracellular, secreted, and membrane-bound forms of hCG CTP """"""""conjugated"""""""" polyproteins; 3) determining that the polyproteins are antigenic; 4) recombining multimeric genes encoding antigenic hCG CTP polyproteins in vaccinia virus. Phase II will involve: 1) constructing (if necessary) further recombinant hCG-vaccinia; 2) cloning cDNA copies of the baboon CG (bCG) gene to allow proper primate studies of vaccine efficacy and safety; 3) testing the ability of each hCG- and bCG-vaccinia vaccine to raise antisera in rabbits that neutralize hCG activity in in vitro and in vivo rat bioassays; 4) initiating baboon studies of neutralizing bCG- and hCG-vaccinia contraceptive vaccines. The polyprotein technology developed here is applicable to any subunit or vaccinia vaccine, and this work is a model for vaccinia vaccines against any autoantigen.
