The contraceptive pill was introduced more than 60 years ago and has proven to be very effective for many women yet existing methods of contraception are not useful for all. Consequently there is considerable interest in developing new methods of contraception for use in humans and for controlling animal populations.
Contraceptive vaccines are not a new concept and the first report of a human “contraceptive vaccine” was the immunisation of women with semen reported by Baskin in 1932 (1). This was apparently an effective means of contraception. However immunisation with semen is probably not a method that will find favour today and to develop contraceptive vaccines that are useful will require identification of a suitable antigenic target. The suitability of antigenic targets will vary between species but there has been considerable work to develop gamete-specific antigens, such as zona pellucida proteins, as contraceptive vaccine targets. One limitation with gamete-specific targets is that they are likely to be expressed only in one sex.
While searching for the antigenic targets of antisperm antibodies that caused infertility in men we discovered SPRASA, a protein whose expression appeared to be limited to the acrosome of sperm. Subsequently, we have also found that SPRASA is expressed in the oocyte, granulosa cells and in the corpora lutea of multiple mammalian species. Immunisation of female mice with recombinant SPRASA resulted in sterility in 70% of the animals and a reduction in litter size/viability in the remainder. Control immunised animals remained fertile. Knockout mice that have the c-terminal portion of the gene encoding SPRASA (SPACA-3) deleted also have significantly reduced litter sizes compared to controls. We have also found that three percent of infertile women have elevated levels of SPRASA-reactive autoantibodies.
Together these data suggest SPRASA may be a suitable target for the immune-based control of fertility.