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Antifertility Vaccines

  • Chapter
Vaccines

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 133))

Abstract

The notion that fertility might be disrupted by immunological mechanisms was conceived nearly a century ago (Landsteiner 1899; METCHINIKOFF 1899). During the next three or four decades numerous studies in animals and humans supported this contention, but there was insufficient understanding of the reproductive and immune systems to seriously pursue the development of a product or procedure for use as a practical antifertility method. Towards the middle of the twentieth century immunologists were beginning to obtain an understanding of the concept of tolerance to self antigens and means to alter antigens to render them immunogenic (CINADER and DUBERT 1955; BURNETT 1961; MEDAWAR 1961). Simultaneously, reproductive scientists began to define the precise function and chemical structure of certain antigens vital for successful reproduction (CLOSSET et al. 1973; MORGAN et al. 1973). These pioneering research contributions led to serious consideration of the potential for developing a safe and effective antifertility method based upon immunological principles during the past three decades.

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References

  • Ada GL, Griffin PD (1991) Vaccines for fertility regulation:the assessment of their safety and efficacy. Cambridge University Press, Cambridge

    Google Scholar 

  • Aitken RJ, Paterson M, Koothan PT (1993) Contraceptive vaccines. Br Med Bull 49:88–99

    PubMed  CAS  Google Scholar 

  • Allardyce RA (1984) Effect of ingested sperm on fecundity in the rat. J Exp Med 159:1548–1553

    Article  PubMed  CAS  Google Scholar 

  • Archibong AE, Lee CY, Wolf DP (1995) Functional characterization of the primate sperm acrosomal antigen (PSA-63). J Androl 16:318–236

    PubMed  CAS  Google Scholar 

  • Awoniyi CA, Kim WK, Hurst BS, Schalff WD (1992) Immunoneutralization of gonadotropin-releasing hormone and subsequent treatment with testosterone Silastic implants in rats:an approach toward developing a male contraceptive. Fertil Steril 58(2):403–408

    PubMed  CAS  Google Scholar 

  • Barfield A, Melo J, Coutinho E, Alvarez-Sanchez F, Faundres A, Brache V, Leon P, Frick J, Bartsch G, Weiske WH, Berner P, Mishell D Jr, Bernstein G, Ortiz A (1979) Pregnancies associated with sperm concentrations below 10 million/ml in clinical studies of a potential male contraceptive method, monthly depot medroxyprogesterone acetatez and testosterone esters. Contraception 20:121–127

    Article  PubMed  CAS  Google Scholar 

  • Baskin MJ (1932) Temporary sterilization by the injection of human spermatozoa (a preliminary report). Am J Obstet Gynecol 24:892

    Google Scholar 

  • Bonduelle ML, Dodd R, Liebaers I, VanSteirteghem A, Williamson R, Akhurst R (1988) Chorionic gonadotropin-β mRNA, a trophoblast marker, is expressed in human 8-cell embryos derived from tripronucleate zygotes. Hum Reprod 3:909–914

    PubMed  CAS  Google Scholar 

  • Burnett FM (1961) Immunological recognition of self. Science 133:307

    Article  Google Scholar 

  • Butterstein GM, Sachar D, Dias JA (1993) Immunoneutralization of heterodimeric FSH using FSH beta subunit as the immunogen. J Reprod Immunol 29:48–55

    CAS  Google Scholar 

  • Cinader B, Dubert JM (1955) Acquired immune tolerance to human albumin and the response to subsequent injections of diazo human albumin. J Exp Pathol (Oxford) 36:515–529

    CAS  Google Scholar 

  • Closset J, Hennen G, Lequin RM (1973) Human luteinizing hormone:the amino acid sequence of the beta subunit FEBS Lett 29:97–100

    CAS  Google Scholar 

  • Coonrod SA, Westhusin ME, Naz RK (1994) Monoclonal antibody to human fertilization antigen (FA-1) inhibits bovine fertilization in vivo:application in immune-contraception. Biol Reprod 51:14–23

    Article  PubMed  CAS  Google Scholar 

  • Cunningham GR, Huckins C (1979) Persistence of complete spermatogenesis in the presence of low intratesticular concentrations of testosterone. Endocrinology 105:177–186

    Article  PubMed  CAS  Google Scholar 

  • Dean J (1992) Biology of mammalian fertilization:role of the zona pellucida. J Clin Invest 89:1055–1059

    Article  PubMed  CAS  Google Scholar 

  • Dean J, Millar SE (1990) Zona pellucida:target for a contraceptive vaccine. In:Alexander NJ, Griffin D, Spieler JM, Waites GMH (eds) Gamete interaction:prospects for immunocontraception. Wiley-Liss, New York, pp 226–313

    Google Scholar 

  • Diczfalusy E (1974) Steps in the human reproductive process susceptible to immunological interference. In:Diczfalusy E (ed) Immunological approaches to fertility control. Karolinska Institutet, Stockholm, pp 13–36

    Google Scholar 

  • Dimitriadou F, Phocas I, Mantazavinos T, Sarandakou A, Rizos D, Zourlas P (1992) Discordant secretion of pregnancy specific β -glycoprotein and human chorionic gonadotropin by human pre-embryos cultured in vitro. Fértil Steril 57:631–636

    PubMed  CAS  Google Scholar 

  • Dunbar BS, Lo C, Powell J, Stevens VC (1989) Use of a synthetic peptide adjuvant for the immunization of baboons with denatured and deglycosylated pig zona pellucida glycoproteins. Fertil Steril 52:311–318

    PubMed  CAS  Google Scholar 

  • Drew MD, Rosenthal KL, McDermott MR (1993) The design of vaccines for inducing secretory immunity in the reproductive tract. In:Griffin PD, Johnson PM (eds) Local immunity in reproductive tract tissues. Oxford University Press, Oxford, pp 484–514

    Google Scholar 

  • Edwards RG (1976) Immunity and the control of human fertility. In:Scott JS, Jones WR (eds) Immunology of human reproduction. Grune & Stratton, New York, pp 415–470

    Google Scholar 

  • Edwards RG, Johnson MH (1976) Physiological effects of immunity against reproductive hormones. Cambridge University Press, London

    Google Scholar 

  • Fraser HM, Gunn A, Jeffcoate SL, Holldan, DT (1974) Effect of active immunization to luteinizing hormone releasing hormone on serum and pituitary gonadotropins, testes and accessory sex organs in the male rat. J Endocrinol 63:399–406

    Article  PubMed  CAS  Google Scholar 

  • Fuchs T, Hammarstrom L, Smith CI, Brundin J (1982) Sex dependent induction of human suppressor T cells by chorionic gonadotropin. J Reprod Immunol 4:185–190

    Article  PubMed  CAS  Google Scholar 

  • Griffin PD, Jones WR, Stevens VC (1994) Anti-fertility vaccines:current status and implications for family planning programmes. Reprod Health Matters 3:108–113

    Google Scholar 

  • Henderson CJ, Hulme MJ, Aitken RJ (1988) Contraceptive potential of antibodies to zona pellucida. J Reprod Fértil 83:325–243

    Article  PubMed  CAS  Google Scholar 

  • Henle W, Henle G, Church CF, Foster I (1940) Spermatozoal antibodies and fertility:attempts to induce temporary sterility in female white mice by passive immunization with spermatoxoal antisera. J Immunol 38:97

    Google Scholar 

  • Herr JC, Wright RM, John E, Foster J, Kays T, Flickinger CJ (1990) Identification of human acrosomal antigen SP-10 in primate and pigs. Biol Reprod 42:377–382

    Article  PubMed  CAS  Google Scholar 

  • Jayaraman KS (1995) India forges ahead with contraceptive vaccine. Nat Med 1(7):609–610

    Article  CAS  Google Scholar 

  • Jin M (1994) Anti- oocyte-antibodies as candidates for immuno-contraception. Thesis, Uppsala University

    Google Scholar 

  • Jin M, Nilsson OB (1992) Enhanced production of monoclonal antibodies against zona-free, unfertilized mouse oocytes by intra-splenic immunization. Hybridoma 11:689–699

    Article  PubMed  CAS  Google Scholar 

  • Johnsen SG (1966) A study of human testicular function by the use of human menopausal gonadotropin and of human chorionic gonadotrophin in male hypogonadotrophic eunuchoidism and infantilism. Acta Endocr 53:489

    Google Scholar 

  • Jones GR, Sacco AG, Subramanian MG Kruger M, Zhang S, Yurewicz EC, Moghissi KS (1992) Histology of ovaries of female rabbits immunized with deglycosylated zona pellucida manromolecules of pigs. J Reprod Fertil 95:513–525

    Article  PubMed  CAS  Google Scholar 

  • Jones WR (1982) Immunological fertility regulation. Blackwell Scientific, Oxford

    Google Scholar 

  • Jones WR (1995) Anti fertility vaccines. In:Nilsson O, Mattsson R (eds) Frontiers in endocrinology:immunocontraception. Ares-Serono Symposia, Rome, pp 5–21

    Google Scholar 

  • Jones WR, Judd SJ, Ing RMY, Powell JE, Bradley J, Denholm EH, Mueller UW, Griffin PD, Stevens VC (1988) Phase I clinical trial of a World Health Organization birth control vaccine. Lancet 1:1295–1298

    Article  PubMed  CAS  Google Scholar 

  • Kaumaya PTP, Kobs-Conrad S, Seo YH, Lee H, VanBuskirk AM, Feng N, Sheridan JF, Stevens VC (1993) Peptide vaccines incorporating a ‘promiscuous’ T-cell epitope bypass certain haplotype restricted immune responses and provide broad spectrum immunogenicity. J Mol Recognit 6:81–94

    Article  PubMed  CAS  Google Scholar 

  • Ladd A, Tsong YY, Prabhu G, Thau R (1989) Effects of long-term immunization against LHRH and androgen treatment on gonadal function. J Reprod Immunol 5:85–101

    Article  Google Scholar 

  • Ladd A, Tsong YY, Walfield, Thau, R (1994) Development of an antifertility vaccine for pets based on active immunization against luteinizing hormone-releasing hormone. Biol Reprod 51:1076–1083

    Article  PubMed  CAS  Google Scholar 

  • Landsteiner K (1899) Zur Kenntnis der spezifisch Auf Blukorperchen wirkenden Sera. Zentralbl Baktiol 25:546–558

    Google Scholar 

  • Lee C-YG, Liu M-S, Su M-W, Zhu JB (1990) Studies of sperm antigens reactive to HS- 11 & JS-63 monoclonal antibodies. In:Alexander NJ, Griffin D, Speiler JM, Waites GMH (eds) Gamete interaction:prospects for immunocontraception, Wiley-Liss, New York, pp 37–51

    Google Scholar 

  • Leyton L, Sailing P (1989) 95kD sperm proteins bind ZP3 and serve as tyrosine kinase substrates in response to zona binding. Cell 57:1123–1130

    Article  PubMed  CAS  Google Scholar 

  • Medawar PB (1961) Immunological tolerance. Science 133:303

    Article  PubMed  CAS  Google Scholar 

  • Meloen RH, Turkstra JA, Lankhof WC, Puijk WC, Schaaper WMM, Dijkstra G, Wensing CJG, Oonk RB (1994) Efficient immunocastration of male piglets by immunoneutralization of GnRH using a new GnRH-like peptide. Vaccine 12:741–746.

    Article  PubMed  CAS  Google Scholar 

  • Metchinikoff E (1899) Etudes sur la resortion des cellules. Ann Inst Pasteur 13:737–746

    Google Scholar 

  • Milwidsky A, Finci-Yeheskel Z, Yagel S, Mayer, M (1993) Gonadotropin-mediated inhibition of proteolytic enzymes produced by human trophoblast in culture. J Clin Endocrinol Metab 76:1101–1105

    Article  PubMed  CAS  Google Scholar 

  • Molenaar GJ, Lugard-Kok C, Meloen RH, Oonk RB, de Koning, J, Wensing CJG (1993) Lesions in the hypothalamus after active immunisation against GnRH in the pig. J Neuroimmunol 48:1–11

    Article  PubMed  CAS  Google Scholar 

  • Morgan FJ, Birken S, Canfield RE (1973) Human chorionic gonadotropin:a proposal for the animo acid sequence. Mol Cell Biochem 2:97–99

    Article  PubMed  CAS  Google Scholar 

  • Moudgal NR (1981) A need for FSH in maintaining fertility of adult male subhuman primates. Arch Androl 7:117–125

    Article  PubMed  CAS  Google Scholar 

  • Naz R, Menge A (1990) Development of antisperm contraceptive vaccines for humans:why and how? Hum Reprod 5:511–518

    PubMed  CAS  Google Scholar 

  • Naz RK, Ahmad K, Kumar R (1991) Human spermatozoa FA-I binds with ZP3 of porcine zona pellucida. J Reprod Immunol 20:43–58

    Article  PubMed  CAS  Google Scholar 

  • O’Hern PA, Bambra CS, Ishakia M, Goldberg E (1995) Reversible contraception in female baboons immunized with a synthetic epitope of sperm-specific lactate dehydrogenase. Biol Reprod 52:331–339

    Article  PubMed  Google Scholar 

  • O’Rand MG, Widgren EE, Nikolajezk BS, Richardson RT, Shabanowitz RB (1990) Receptors for zona pellucida on sperm. In:Alexander NJ, Griffin D, Spieler JM, Waites GMH (eds) Gamete interaction:prospects for immunocontraception. Wiley-Liss, New York, pp 213–224

    Google Scholar 

  • Parr EL, Parr, MB (1993) Local immunization for antifertility immunity. In:Griffin PD, Johnson PM (eds) Local immunity in reproductive tract tissues. Oxford University Press, Oxford, pp 441–458

    Google Scholar 

  • Pearlman P (1954) Study on the effect of antisera on unfertilized sea urchin eggs. Exp Cell Res 6:485

    Article  Google Scholar 

  • Perez-Martinez S, Conesa D, Cuasrucu PD (1995) Potential contraceptive use of epididymal proteins:evidence for the participation of specific antibodies against rat epididymal protein DE in male and female fertility inhibition. J Reprod Immunol 29:31–45

    Article  PubMed  CAS  Google Scholar 

  • Prasad SV, Mujtake S, Lee VH, Dunbar BS (1995) Immunogenicity enhancement of recombinant rabbit 55-kilodalton zona pellucida protein expressed using the baculovirus expression system. Biol Reprod 52:467–478

    Article  Google Scholar 

  • Primakoff P, Myles DG (1990) Progress towards a birth control vaccine that blocks sperm function. In:Alexander NJ, Griffin D, Speiler JM, Waites GMH (eds) Gamete interaction:prospects for immunocontraception, Wiley-Liss, New York pp 89–102

    Google Scholar 

  • Primakoff P, Lathrop W, Woolman L, Cowen L, Myles D (1988) Fully effective contraception in male and female guinea pigs immunized with the sperm protein PH-20. Nature 335:543–546

    Article  PubMed  CAS  Google Scholar 

  • Raj HGM, Murty GSRC, Sairam MR, Talbert LM (1982) Control of spermatogenesis in primates:effects of active immunization against FSH in the monkey. Int J Androl [Suppl] 5:27–33

    Article  CAS  Google Scholar 

  • Ramarao CS, Myles DG, Primakoff P (1994) Multiple roles for Ph-20 and fertilin in sperm-egg interaction. Dev Biol 5:265–271

    Google Scholar 

  • Rhim SH, Millar SE, Robey F, Lau AM, Lou YH, Yule T, Allen P, Dang J, Tung KSK (1992) Autoimmune disease of the ovary induced by a ZP3 peptide from the mouse zona pellucida. J Clin Invest 89:28–35

    Article  PubMed  CAS  Google Scholar 

  • Sacco A (1987) The zona pellucida:current status as a candidate antigen for contraceptive vaccine development. J Reprod Immunol 15:122–130

    CAS  Google Scholar 

  • Sacco AG, Yurewicz EC, Subramaniaan MG, deMayo FJ, Dukelow (1991) Immunologic response and ovarian histology of squirrel monkeys (Saimeri sciureus) immunized with porcine zona pellucida ZP3 macromolecules. Am J Primatol 24:15–28

    Article  Google Scholar 

  • Schwoebel ED, Vandervoort CA, Lee VH, Lo YK, Dunbar BS (1992) Molecular analysis of the antigenicity and immunogenicity of recombinant zona pellucida antigens in a primate model. Biol Reprod 47:857–865

    Article  PubMed  CAS  Google Scholar 

  • Sherins RJ (1974) Clinical aspects of treatment of male infertility with gonadotrophins:testicular response of some men given hCG with and without Pergonal. In:Mancini RE, Martini L (eds) Male fertility and sterility. Raven, New York, pp 545–556

    Google Scholar 

  • Shivers CA (1974) Immunological interference with fertilization. In:Diczfalusy E (ed) Immunological approaches to fertility control. Karolinska Institutet, Stockholm, pp 223–244

    Google Scholar 

  • Shivers CA, Dunbar BS (1977) Auto antibodies to zona pellucida:a possible cause for infertility in women. Science 192:1082–1084

    Article  Google Scholar 

  • Singh O, Rao LV, Gaur A, Sharma NC, Alam A, Talwar GP (1989) Antibody response and characteristics of antibodies in women immunized with three contraceptive vaccines inducing antibodies against human chorionic gonadotropin. Fertil Steril 52:739–744

    PubMed  CAS  Google Scholar 

  • Srinivasan J, Tinge S, Wright R, Herr JC, Curtiss III R (1995) Oral immunization with attenuated Salmonella expressing human sperm antigen induces antibodies in serum and the reproductive tract. Biol Reprod 53:462–471

    Article  PubMed  CAS  Google Scholar 

  • Stevens VC (1992) Future perspectives for vaccine development. Scand J Immunol 36 [Suppl 11]:137–143

    Article  Google Scholar 

  • Stevens VC (1996) Progress in the development of human chorionic gonadotropin antifertility vaccines. J Reprod Immunol 35:148–155

    Article  CAS  Google Scholar 

  • Stevens VC, Chou WS, Powell JE, Lee AC, Smoot J (1986) The identification of peptide sequences of human chorionic gonadotropin containing a conformational epitope. Immunol Lett 12:11–18

    Article  PubMed  CAS  Google Scholar 

  • Stevens VC, Powell JE, Lee AE, Kaumaya PTP, Lewis DH, Rickey M, Atkins TJ (1992) Development of a delivery system for a birth control vaccine using biodegradable microspheres. In:Kopecek (ed) Proceedings of the 19th International Symposium on Controlled Release of Bioactive Materials. Controlled Release Society, Orlando, pp 112–113

    Google Scholar 

  • Stewart DR, Overstreet JW, Nakajima ST, Lasley BL (1993) Enhanced ovarian steroid secretion before implantation in early human pregnancy. J Clin Endocrinol Metab 76:1470–1476

    Article  PubMed  CAS  Google Scholar 

  • Suri A, Talwar GP, Shaba C (1993) Oral immunization with sperm antigens. In:Griffin PD, Johnson PM (eds) Local immunity in reproductive tract tissues. Oxford University Press, Oxford, pp 427–440

    Google Scholar 

  • Suri A, Chhabra S, Upadhay S (1996) Identification of human sperm antigen recognized by serum of an immunoinfertile woman:a candidate for immunocontraception. J Reprod Immunol 36:317–326

    Article  CAS  Google Scholar 

  • Talwar GP, Singh O, Pal R, Chatterjee N, Sahai P, Dhall K, Kaur J, Das SK, Suri S, Buckshee K, Saraya L, Saxena BN (1994) A vaccine that prevents pregnancy in women. Proc Natl Acad Sci USA 91:8532–8536

    Article  PubMed  CAS  Google Scholar 

  • Tung KSK, Lou Y-H, Luo A-M, Ang J (1994) Contraceptive vaccine assessment based on murine ZP3 mini-autoantigen. Reprod Fertil Dev 6:340–355

    Article  Google Scholar 

  • Westhoff WE, Slootstra JW, Puijk WC, Kuperus D, Flinterman JF, Schaaper WMM, Oonk HB, Meloen RH (1996) Detection of epitopes on follicle-stimulating hormone and FSH-antiserum-induced suppression of bioactivity of follicle- stimulating hormone and luteinizing hormone. J Reprod Immunol 30:133–149

    Article  PubMed  CAS  Google Scholar 

  • Wickings EJ, Usadel KH, Dathe G, Nieschlag E (1980) The role of follicle-stimulating hormone in testicular function of the mature rhesus monkey. Acta Endocr 95–117

    Google Scholar 

  • Wright RM, Suri AK, Komreich B, Flinkenger CJ, Herr JC (1993) Cloning and characterization of the gene coding for the human acrosomal protein SP-10. Biol Reprod 49:316–325

    Article  PubMed  CAS  Google Scholar 

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  1. V. C. Stevens
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Editors and Affiliations

  1. The Wenner-Gren Institute Department of Immunology The Arrhenius Laboratories F5, Stockholm University, S-106 91, Stockholm, Sweden

    Peter Perlmann (Professor) (Professor)

  2. MTC, Karolinska Institute, S-171 77, Stockholm, Sweden

    Hans Wigzell (Professor) (Professor)

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© 1999 Springer-Verlag Berlin Heidelberg

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Stevens, V.C. (1999). Antifertility Vaccines. In: Perlmann, P., Wigzell, H. (eds) Vaccines. Handbook of Experimental Pharmacology, vol 133. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-59955-2_16

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  • DOI: https://doi.org/10.1007/978-3-642-59955-2_16

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