This minireview summarizes the main data relevant to the development of
contraceptive vaccines based on zona pellucida (ZP)
antigens, as well as the pros and the cons of this immunocontraceptive strategy. Even though the antifertility efficacy of anti-ZP
antibodies in humans is not corroborated by a clear relationship between spontaneous autoimmunization against the ZP and
infertility, passive and active immunization studies in laboratory animals have provided convincing results. The
contraceptive action of anti-ZP
antibodies, targeting events situated upstream of gamete fusion, is devoid of potential ethical concerns related to the destruction of early embryos. The high
protein content of the mammalian ZP, knowledge of the complete amino acid sequence of the major
ZP proteins, and the high degree of sequence homology between individual species all favour the rapid advancement of anti-ZP
vaccine projects. However, certain sequences of
ZP proteins, when incorporated into the
vaccine construct, activate CD4+ T cells of the recipient organism to direct a cellular immune attack (
autoimmune oophoritis) to other functionally relevant ovarian components (primordial follicles, steroidogenic cells). The search for the optimal combination of B cell and
T cell epitopes in the
vaccine construct will hopefully overcome this problem.