Immunocontraception with zona pellucida proteins.
The prospect of an immunological approach to contraception that would disrupt the process of fertilisation itself has resulted in a considerable interest into research in this area. It has been known for some time that antibodies raised against the zona pellucida (ZP) can suppress fertility very effectively. However, the initial optimism of this approach has been marred by the appearance of an ovarian pathology characterised by disruption of folliculogenesis and depletion of the primordial follicle pool. Adverse auto-immune reactions have been observed in the ovaries of mice after the induction of immunity with mouse ZP3 epitopes. However, this was associated with lymphocytic infiltration of the ovarian stroma, which could be circumvented by careful selection of B-cell epitopes to induce reversible infertility. In order to identify similar epitopes on primate ZP3, epitope-mapping studies were performed and incorporated into chimeric vaccines that included a promiscuous T-helper cell epitope. Both single and triple peptide vaccines have been evaluated in vivo and no detrimental effects on ovarian function were observed. The resulting high titre antibodies bound exclusively to the ZP of marmoset and human ovarian sections and could suppress in vitro human sperm-egg binding by approximately 60%, but did not prevent pregnancy in actively immunised female marmosets. Thus, considerable research is still required to identify a combination of ZP3 epitopes that will induce infertility free of any unwanted side effects.
Paterson
M
M
MRC Reproductive Biology Unit, Edinburgh, UK. m.paterson@ed-rbu.mrc.ac.uk
Jennings
Z A
ZA
van Duin
M
M
Aitken
R J
RJ
D000818:Animals; D003269:Contraception, Immunologic; D016326:Extracellular Matrix Proteins / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D011247:Pregnancy; D013084:Sperm-Ovum Interactions; D015044:Zona Pellucida / Q000502:physiology*
D016326:Extracellular Matrix Proteins