Intra-Acrosomal Contraceptive Vaccine Immunogen SP-10 in Human, Macaque, and Baboon

  • John C. Herr
  • Richard M. Wright
  • Charles J. Flickinger
  • Alex Freemerman
  • Kenneth Klotz
  • James Foster
  • John Shannon
Conference paper
Part of the Serono Symposia, USA book series (SERONOSYMP)

Abstract

SP-10 is an acrosomal protein that is first detected within the developing acrosome of round spermatids in the human testis and persists within the acrosome of mature spermatozoa (1, 2). SP-10 has been designated a primary contraceptive vaccine candidate by a WHO task force on contraceptive vaccines on the basis of several characteristics (3). First, current tissue specificity data suggest that SP-10 is specific to maturing germ cells within the testis (1, 4, 5). Such tissue specificity reduces the likelihood of autoimmune disease arising in females who are administered an SP-10 vaccine. Second, SP-10 has been detected in the sperm of all human males tested to date (N > 200) and thus appears to be conserved among men (2). Third, SP-10 remains associated with the sperm head after the acrosome reaction (2). Finally, a monoclonal antibody to SP-10 (MHS-10) was shown to inhibit human sperm penetration in the hamster egg penetration assay (3). Additional preliminary data have shown human IVF to be inhibited by a monoclonal antibody that reacts with a molecule considered to be SP-10 (6).

Keywords

Hydrolysis HPLC Codon Glycine Carboxyl 

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References

  1. 1.
    Kurth BE, Klotz K, Flickinger CJ, Herr JC. Localization of sperm antigen SP-10 during the six stages of the cycle of the seminiferous epithelium in man. Biol Reprod 1991;44:814–821.PubMedCrossRefGoogle Scholar
  2. 2.
    Herr JC, Flickinger CJ, Homyk M, Klotz K, John E. Biochemical and morphological characterization of the intra-acrosomal antigen SP-10 from human sperm. Biol Reprod 1990;42:181–193.PubMedCrossRefGoogle Scholar
  3. 3.
    Anderson DJ, Johnson PM, Jones WR, Griffen PD. Monoclonal antibodies to human trophoblast and sperm antigens: report of two WHO-sponsored workshops, June 30, 1986, Toronto, Canada. J Reprod Immunol 1987; 10:231–257.PubMedCrossRefGoogle Scholar
  4. 4.
    Wright RM, John E, Klotz K, Flickinger CJ, Herr JC. Cloning and sequencing of cDNAs coding for the human intra-acrosomal antigen SP-10. Biol Reprod 1990;42:693–701.PubMedCrossRefGoogle Scholar
  5. 5.
    Herr JC, Wright RM, John E, Foster J, Kays T, Flickinger CJ. Identification of human acrosomal antigen SP-10 in primates and pigs. Biol Reprod 1990;42:377–382.PubMedCrossRefGoogle Scholar
  6. 6.
    Dubova-Mihailova M, Mollova M, Ivanova M, Kehayov I, Kyurkchiev S. Identification and characterization of human acrosomal antigen defined by a monoclonal antibody with blocking effect on in vitro fertilization. J Reprod Immunol 1991;19:251–268.PubMedCrossRefGoogle Scholar
  7. 7.
    Kozac M. Compilation and analysis of sequences upstream from the translational start site in eukaryotic mRNAs. Nucleic Acids Res 1984;12:857–873.CrossRefGoogle Scholar
  8. 8.
    Pless DD, Lennarz WJ. Enzymatic conversion of proteins to glycoproteins. Proc Natl Acad Sci USA 1977;74:134–138.PubMedCrossRefGoogle Scholar
  9. 9.
    Hart GW, Brew K, Grant GA, Bradshaw RA, Lennarz WJ. Primary structural requirements for the enzymatic formation of the N-glycosidic bond in glycoprotein studies with natural and synthetic peptides. J Biol Chem 1979;254:9747–9753.PubMedGoogle Scholar
  10. 10.
    von Heijne G. A new method for predicting signal sequence cleavage sites. Nucleic Acids Res 1986;14:4683–4690.CrossRefGoogle Scholar
  11. 11.
    Liu MS, Ruedi A, Lee CYG. Molecular and developmental studies of a sperm antigen recognized by HS-63 monoclonal antibody. Biol Reprod 1992;46:937–948.PubMedCrossRefGoogle Scholar
  12. 12.
    Stevens VC, Powell JE, Lee AC, Griffin D. Antifertility effects of immunization of female baboons with C-terminal peptides of the ß-subunit of human chorionic gonadotropin. Fertil Steril 1981;36:98–105.PubMedGoogle Scholar
  13. 13.
    Herr JC, Klotz K, Shannon J, Wright RM, Flickinger CJ. Purification and microsequencing of the intra-acrosomal protein SP-10: evidence that SP-10 heterogeneity results from endoproteolytic processes. Biol Reprod 1992;46:981–990.PubMedCrossRefGoogle Scholar
  14. 14.
    Primakoff P, Hyatt H, Tredick-Klein J. Identification and purification of a sperm surface protein with a potential role in sperm-egg membrane fusion. J Cell Biol 1987;104:141–149.PubMedCrossRefGoogle Scholar
  15. 15.
    Primakoff P, Cowan A, Hyatt H, Tredick-Klein J, Myles D. Purification of the guinea pig sperm PH20 antigen and detection of a site-specific endoproteolytic activity in sperm preparations that cleaves PH20 into two disulfide-linked fragments. Biol Reprod 1988;38:921–934.PubMedCrossRefGoogle Scholar
  16. 16.
    Baba T, Kashiwabara S, Watanabe K, et al. Activation and maturation mechanisms of boar acrosin zymogen based on the deduced primary structure. J Biol Chem 1989;264:11920–11927.PubMedGoogle Scholar
  17. 17.
    Polakoski KL, Parrish RF. Boar proacrosin. Purification and preliminary activation studies of proacrosin isolated from ejaculated boar sperm. J Biol Chem 1977;252:1888–1894. PubMedGoogle Scholar
  18. 18.
    Parrish RF, Polakoski KL. Boar Ma-acrosine. Purification and characterization of the initial active enzyme resulting from the conversion of boar proacrosin to acrosin. J Biol Chem 1978;253:8428–8432. PubMedGoogle Scholar
  19. 19.
    Orlowski M, Wilk E, Pearce S, Wilk S. Purification and properties of a prolyl endopeptidase from rabbit brain. J Neurochem 1979;33:461–469.PubMedCrossRefGoogle Scholar
  20. 20.
    Saling PM. Mammalian sperm interaction with extracellular matrices of the egg. Oxford Rev Reprod Biol 1989;11:339–388.Google Scholar
  21. 21.
    Siegel MS, Polakoski KL. Evaluation of the human sperm proacrosin-acrosin system using gelatin-sodium dodecylsulfate-polyacrylamide gel electrophoresis. Biol Reprod 1985;32:713–720.PubMedCrossRefGoogle Scholar
  22. 22.
    Siegel MS, Bechtold DS, Kopta CI, Polakoski KL. The rapid purification and partial characterization of human sperm proacrosin using an automated fast protein liquid chromatography (FPLC) system. Biochim Biophys Acta 1986;883:567–573.PubMedGoogle Scholar
  23. 23.
    Elce JS, McIntyre EJ. Acrosin: immunochemical demonstration of multiple forms generated from bovine and human proacrosin. Can J Biochem Cell Biol 1982;61:989–995.CrossRefGoogle Scholar
  24. 24.
    Siegel MS, Polakoski KL. Human sperm proteinases: purification and characterization of proacrosin and a unique zymogen referred to as sperminogen. Biol Reprod;30(suppl 1):177.Google Scholar
  25. 25.
    Siegel MS, Bechtold DS, Willand JL, Polakoski KL. Partial purification and characterization of human sperminogen. Biol Reprod 1987;36:1063–1068.PubMedCrossRefGoogle Scholar
  26. 26.
    Anakwe OO, Gerton G. Acrosome biogenesis begins during meiosis: evidence from the synthesis and distribution of an acrosomal glycoprotein, acrogranin, during guinea pig spermatogenesis. Biol Reprod 1990;42:317–328.PubMedCrossRefGoogle Scholar
  27. 27.
    Rosen J, Tomkinson B, Pettersson G, Zetterqvist O. A human serine endopeptidase, purified with respect to activity against a peptide with phosphoserine in the P1 position, is apparently identical with prolyl endopeptidase. J Biol Chem 1991;266:3827–3834.PubMedGoogle Scholar
  28. 28.
    Freemerman AJ, Wright R, Flickinger CJ, Herr JC. Cloning and sequencing of baboon and cynomolgus monkey intra-acrosomal protein SP-10; homology with human SP-10 and a mouse sperm antigen (MSA-63). Mol Reprod Dev 1992.Google Scholar

Copyright information

© Springer-Verlag New York, Inc 1993

Authors and Affiliations

  • John C. Herr
  • Richard M. Wright
  • Charles J. Flickinger
  • Alex Freemerman
  • Kenneth Klotz
  • James Foster
  • John Shannon

There are no affiliations available

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