The potential use of sperm antigens as targets for immunocontraception; past, present and future

Immunocontraception, and in particular the targeting of antibodies to gamete-specific antigens implicated in sperm egg binding and fertilisation, offers an attractive approach to the growing global problem of overpopulation. Such an idea is not new; indeed several immunocontraception trials, using animal model systems, have been reported in recent years and a number are reviewed here. However, the results of these studies have been largely disappointing. We believe that two fundamental flaws attribute to the poor success of most of these preliminary immunocontraceptive trials. Firstly, loss of fertility has invariably been used as the assay. This presupposes that immuno-neutralisation of a single, gamete-specific antigen will be sufficient to cause a significant reduction in fertility; however, recent data suggests that such a premise may not be well-founded for a number of reasons. Secondly, and arguably the most important flaw, is the almost universal, but largely inappropriate, use of systemic immunisation as the sole route of antigen delivery. Whilst systemic immunisation regimes may lead to high serum IgG levels, these levels do not correlate with specific antibody levels in the reproductive tract or with contraceptive efficacy. Hence, an alternative antigen delivery approach is required which will induce an effective local immune response in the reproductive tract. Here we discuss the ways in which this might be achieved.