Cloning and Sequencing of Sperm Antigens Involved in Oocyte Interaction: Clinical applications in infertility and immunocontraception

Abstract

Sperm-zona pellucida (ZP) recognition and binding constitutes the most important event in the fertilization process and the molecules involved at this site are attractive candidates for the contraceptive vaccine development (CVD). The extensive research indicates that there are four sperm surface proteins that bind to oocyte ZP3 in humans and they belong to four molecular regions of 94 kD, 63 kD, 51 kD and 14-18 kD, respectively (Mol Reprod Develop 1994; 39: 397-408). Our laboratory is actively engaged in cloning and sequencing of the cDNAs encoding for these sperm proteins and investigating the applications of recombinant proteins in CVD and infertility. Presently, the cDNAs encoding for the 14-18 kD proteins, designated NZ-1 and NZ-2, respectively, (Mol Reprod Develop 1997; 48: 449-457; ibid, 1998; 51: 176-183) and the 51 kD protein, designated fertiliztion antigen (FA-1) (Proc Natl Acad Sci USA 1997; 94: 4704-4709) have been cloned and sequenced. Antibodies to the recombinant proteins showed a block/inhibition of sperm-ZP binding in the in vitro assays. Active immunization with the recombinant FA-1 antigen caused a reversible (up to 8-9 months) inhibition in fertility of female mice by raising a sperm/testis-specific immune response. FA-1 antigen is also involved in human immunoinfertility. The recent clinical trial being conducted at the University of Michigan indicates that it will have clinical application in the treatment of immunoinfertile man. These findings suggest that the recombinant sperm antigens when used in a single formulation, will generate an antisperm vaccine that is strongly immunogenic and highly efficacious for contraception.