The need for new effective means of contraception is great. Experience with rodents and domestic animals suggests that sperm surface antigens can serve as immunocontraceptive vaccines. The efficacy of such an approach to contraception should be evaluated in nonhuman primates as a logical step in the development of this technology for human application. This proposal is designed to probe the primate sperm surface for antigenic components that could serve as immunocontraceptive vaccine candidates. The ability to measure sperm function in vitro including fertilization is critical to the selection of vaccine candidates. While assessments of human sperm motility and acrosomal status are possible by in vitro approaches, the fertilization of human oocytes is precluded on the basis of ethical and practical concerns. A major rationale for the present study in the rhesus monkey is that the assessment of sperm function and in vitro fertilization in this species is highly relevant to the human case.
Four specific aims are proposed: (1) to generate a library of monoclonal antibodies against rhesus monkey sperm surface antigens using purified sperm plasma membrane preparations as immunogens; (2) to screen for monoclonal anti-rhesus monkey sperm antibodies that cross react with human sperm and inhibit in vitro assays of primate sperm function (the latter include specific parameters of motility, hyperactivation, acrosomal status, and zona binding/penetration); (3) to demonstrate that selected monoclonal antisperm antibodies inhibit the in vitro fertilization of rhesus monkey oocytes; and (4) to characterize target sperm surface antigens and conduct feasibility assessments on their use as immunogens. These studies should result in the identification of primate sperm surface components with antigenic determinants shared between the rhesus monkey and man. The proposed isolation and characterization of surface antigens will allow the final selection of immunocontraceptive vaccine candidates. The results generated should support future efforts to produce large amounts of selected sperm surface antigens by recombinant DNA technology and to conduct contraceptive efficacy trials in actively immunized rhesus monkeys.
| Archibong, A E; Lee, C Y; Wolf, D P (1995) Functional characterization of the primate sperm acrosomal antigen (PSA-63). J Androl 16:318-26 |
| Lanzendorf, S E; Gliessman, P M; Archibong, A E et al. (1990) Collection and quality of rhesus monkey semen. Mol Reprod Dev 25:61-6 |
| Dalkin, A C; Haisenleder, D J; Ortolano, G A et al. (1989) The frequency of gonadotropin-releasing-hormone stimulation differentially regulates gonadotropin subunit messenger ribonucleic acid expression. Endocrinology 125:917-24 |
| Wolf, D P; Vandevoort, C A; Meyer-Haas, G R et al. (1989) In vitro fertilization and embryo transfer in the rhesus monkey. Biol Reprod 41:335-46 |
