Development of contraceptive vaccines for humans using antigens derived from gametes (spermatozoa and zona pellucida) and hormones (human chorionic gonadotrophin): current status

Abstract

Contraceptive research has entered a new phase of development with the advent of hybridoma and DNA recombinant technologies. During the past 5 years, significant advances have been made in this area and now it seems that realistic prospects exist for the development of contraceptive vaccines for use in humans and animals (veterinary, wild and domestic), applicable to both the female and male sexes. Contraceptive vaccines will be valuable supplements to the presently available methods of family planning, and, due to high specificity, the occurrence of limited side-effects if any, low cost and infrequent administration, contraceptive vaccines may have greater acceptability than the currently available methods. Mammalian reproduction starts with the unison of gametes contributed by the male and female partners. Both spermatozoon and oocyte have antigens on the cell surface that are unique, tissue-specific, immunogenic and accessible to antibodies, and binding of the antibodies to these antigens can cause inhibition of gamete function, resulting in a failure of fertilization. Fertilization is followed by embryogenesis, with the early embryo producing several proteins, some of which, e.g. human chorionic gonadotrophin (HCG), have a vital role in the establishment and maintenance of early pregnancy. Again, these proteins are accessible to antibodies, and their immunoneutralization can cause anti-fertility effects with loss of early embryo. Thus, the antigens derived from proteins on spermatozoa, oocyte and early embryo, especially HCG, constitute interesting molecules for the development of contraceptive vaccines. The aim of the present article is to review the current status of development of contraceptive vaccines based on antigens derived from sperm cell, oocyte zona pellucida and HCG, and to discuss their relative merits and future development.

Identification of Human Sperm Peptide Sequence Involved in Egg Bindingfor Immunocontraception1

“…Development of a vaccine based on sperm antigens represents a promising approach to contraception [1,2]. The rationale and feasibility of this approach are provided by experimental immunization studies as well as data from involuntary infertility and vasectomy.…”

“…Thus, the sperm cell has both auto-and iso-antigenic potentials and can generate an immune response in both men and women that is capable of inducing infertility. 1 Supported in part by NIH grant HD24425 to R.K.N. No funds from this grant were used for human IVF and for studies involving human oocyte zona pellucida.…”

“…2 Correspondence: Rajesh K. Naz The utility of a sperm antigen in the development of a contraceptive vaccine is contingent on its involvement in the fertilization process and on tissue specificity. During the past decade, several antigens relevant to fertility have been defined (reviewed in [1]). A few of these also affect fertility in actively immunized animals [1,13].…”

Potential Contraceptive Use of Epididymal Proteins: Immunization of Male Rats with Epididymal Protein DE Inhibits Sperm Fusion Ability1

“…Numerous reports have clearly shown the relationship between immunization with sperm components and reduction of fertility [1,2]. Most of the studies have been carried out using sperm proteins of testicular origin, and little information exists regarding the use of epididymal components.…”

Sperm Surface Protein Profiles of Fertile and Infertile Men: Search for a Diagnostic Molecular Marker

“…Several proteins that are involved in sperm structure and function are being defined and characterized, and the complementary DNAs encoding for these proteins are being cloned and sequenced in several mammalian species, including humans [5,7,14,15]. The molecules involved in tyrosine phosphorylation leading to sperm capacitation/acrosome exocytosis and zona pellucida binding are presently being delineated.…”