Vaccination with a synthetic zona pellucida peptide produces long-term contraception in female mice.
The zona pellucida surrounding mouse oocytes is an extracellular matrix composed of three sulfated glycoproteins, ZP1, ZP2, and ZP3. It has been demonstrated that a monoclonal antibody to ZP3 injected into female mice inhibits fertilization by binding to the zona pellucida and blocking sperm penetration. A complementary DNA encoding ZP3 was randomly cleaved and 200- to 1000-base pair fragments were cloned into the expression vector lambda gt11. This epitope library was screened with the aforementioned contraceptive antibody, and the positive clones were used to map the seven-amino acid epitope recognized by the antibody. Female mice were immunized with a synthetic peptide containing this B cell epitope coupled to a carrier protein to provide helper T cell epitopes. The resultant circulating antibodies to ZP3 bound to the zona pellucida of immunized animals and produced long-lasting contraception. The lack of ovarian histopathology or cellular cytotoxicity among the immunized animals may be because of the absence of zona pellucida T cell epitopes in this vaccine.
Millar
S E
SE
Laboratory of Cellular and Developmental Biology, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD 20892.
Chamow
S M
SM
Baur
A W
AW
Oliver
C
C
Robey
F
F
Dean
J
J
D000595:Amino Acid Sequence; D000818:Animals; D000941:Antigens / Q000276:immunology; D001483:Base Sequence; D003001:Cloning, Molecular; D003267:Contraception; D003269:Contraception, Immunologic; D004247:DNA / Q000235:genetics; D004527:Egg Proteins; D000939:Epitopes / Q000032:analysis; D005260:Female; D006023:Glycoproteins / Q000235:genetics / Q000276:immunology*; D008297:Male; D008562:Membrane Glycoproteins; D051379:Mice; D008969:Molecular Sequence Data; D010063:Ovum / Q000502:physiology*; D011487:Protein Conformation; D012333:RNA, Messenger / Q000235:genetics; D011956:Receptors, Cell Surface; D014611:Vaccination; D015044:Zona Pellucida / Q000502:physiology*; D000072216:Zona Pellucida Glycoproteins
D000941:Antigens; D004527:Egg Proteins; D000939:Epitopes; D006023:Glycoproteins; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D000072216:Zona Pellucida Glycoproteins; C000606519:Zp1 protein, mouse; C000606520:Zp2 protein, mouse; C000606521:Zp3 protein, mouse; D004247:DNA