The contraceptive potential of ZP3 and ZP3 peptides in a primate model.
It has been known for some time that antibodies raised against ZP3, the major component of the glycoprotein shell that surrounds all mammalian oocytes, can successfully inhibit sperm-egg interaction in vitro. In our own studies using the non-human primate Callithrix jacchus, active immunisation was successfully achieved when homologous or heterologous ZP3 was used as an immunogen. However this long-term suppression of fertility was at the expense of ovarian function. An ovarian pathology was observed which was characterised by a disruption of folliculogenesis and depletion of the primordial follicle pool. Adverse auto-immune reactions have also been observed in mice following induction of immunity to mouse ZP3. Following careful selection of B-cell epitopes on mouse ZP3, peptide vaccines were formulated which could circumvent these adverse side effects and induce reversible infertility in actively immunised mice. To identify similar epitopes on primate ZP3, epitope mapping studies were performed and several candidate regions of the molecule were identified. These were incorporated into chimeric peptide vaccines and administered as single or triple peptide vaccines. Active immunisation successfully induced antibodies that bound exclusively to the zona pellucida of marmoset and human ovarian sections. These antibodies were able to suppress human sperm-egg binding by up to 60% in vitro. Encouragingly, no adverse side effects on ovarian function were observed following long-term immunisation however, no loss of fertility was consistently observed in vivo. Thus considerable research is still required to identify a combination of ZP epitopes that will induce reversible infertility in the absence of any ovarian dysfunction.
Paterson
Margaret
M
MRC Human Reproductive Sciences Unit, Centre for Reproductive Biology, 37, Chalmers Street, Edinburgh, EH3 9ET, UK. m.paterson@hrsu.mrc.ac.uk
Jennings
Zoë A
ZA
Wilson
Martin R
MR
Aitken
R John
RJ
D000818:Animals; D002144:Callithrix; D003269:Contraception, Immunologic / Q000009:adverse effects; D004527:Egg Proteins / Q000276:immunology*; D000939:Epitopes / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D023421:Models, Animal; D010053:Ovary / Q000473:pathology; D010446:Peptide Fragments / Q000276:immunology; D011956:Receptors, Cell Surface; D013084:Sperm-Ovum Interactions / Q000276:immunology; D014614:Vaccines, Synthetic / Q000494:pharmacology; D015044:Zona Pellucida / Q000276:immunology; D000072216:Zona Pellucida Glycoproteins
D004527:Egg Proteins; D000939:Epitopes; D008562:Membrane Glycoproteins; D010446:Peptide Fragments; D011956:Receptors, Cell Surface; D014614:Vaccines, Synthetic; C000606517:ZP3 protein, human; D000072216:Zona Pellucida Glycoproteins; C000606521:Zp3 protein, mouse