New Perspectives immunocontraception

Immunocontraception with Eppin seems effective and reliable, but its safety need to be further proved(6).  Antibodies to Eppin in immunized male monkeys provide an effective and reversible contraception and these antibodies may be effective by interfering with Eppin’s interaction with semenogelin during ejaculation.  Hydrolysis of semenogelin was performed by prostate specific antigen(7,8).

Immunocontraception and, in particular the targeting of antibodies to gamete-specific antigens implicated in sperm egg binding and fertilization, offers an attractive approach to control fertility.

The antibodies raised against the sperm specific antigens have proved to be extremely effective at reducing sperm-egg interaction in vitro(9). Sperm has been known to be antigenic for more than a century. There is a strong body of evidence that in humans and in other species at least some antibodies that bind to sperm antigen can cause infertility.

These antibodies are of interest because can induce infertility, consequently, they have the potential to be developed for contraceptive purposes in humans and also for the control of feral animal populations(10).  In addition,  epidemiologic studies indicated   that   some   infertile   men   who   were   infected   with   Ureaplasma urealyticum(UU)  displayed positive antisperm antibodies in their serum and/or semen. The existence of cross-reactive antigens (61,50,25kDa)  between UU and human   sperm   membrane   proteins   was   confirmed. 

In   fact,  a   pentapeptide identity (IERLT) was found in anti-rUreG and in antiserum against the synthetic peptide NASP 393-408 and its presence inhibited mouse sperm egg binding and fusion.  After immunization by rUreG or the synthetic peptide, 81.2 and 75% female mice became sterile,  respectively.  Besides,  the effect on fertility in mice immunized with the synthetic peptide was reversible (11,12).

A recombinant ovalbumin–luteinizing hormone–releasing hormone(ova-LHRH)  antigen has been developed for immunocontraception. This vaccine seems an effective immunostimolant for LHRH immunization and contraception(13).

Currently, interest was devoted to sperm-reactive human single chain variable fragment   (scFv) antibodies.  These   antibodies   seem   to   offer   an   available prospective in human sperm function inhibition(14). At the present time, the studies are focused on increasing the immunogenicity and efficacy of the birth control vaccine.  A licit suspect consent to hypotisize that the vaccines may be abused by health advocates in developing countries and by their use in vulnerable groups of population.

Rosa Sabatini and Raffele Cagiano
Department of Obstetrics and Gynecology
Department of Pharmacology General Hospital Policlinico-University of Bari, Italy


  1.   Dirnhofer S.,  Wick G.,  Berger P.  (1995).  The suitability of human chorionic   gonadotropin   (h-CG)-based   birth-control   vaccines.  Immunol Today, 15(10), 469-74. 
  2.   Jones W.R.  (2005). Vaccination   for   contraception.  Aust.N.Z.J. Obstet. Gynecol.  1994;34(3),  320-9.  3)Naz   RK   Contraceptive   vaccines. Drugs, 65(5), 593-603.
  3.   Clauss A., Lilja H., Lundwall A. (2002). A locus on human chromosome 20 contains several genes expressing protease inhibitor domains with homology to whey acid protein. Biochem. J, 368(1), 233-42
  4.   Guo X.Q., Wang R.J. (2005). Advances in the study of epididymal protease inhibitor. Zhonghua Nan. Ke Xue, 11(11), 851-3. ) 
  5.   Richardson R.T., Sivashanmugan P., Hall S.H., Hamil K.G., Moore P.A., Ruben S.M, French F.S., O’ Rand M. (2001). Cloning and sequencing of human Eppin: a novel family of protease inhibitors expressed in the epididymis and testis. Gene, 270(1-2),93-102
  6.   O’Rand M.G., Widgren E.E., Wang Z., Richardson R.T. (2007). Eppin: an epididymal   protease   inhibitor   and   a   target   for   male   contraception. Soc. Reprod. Fertil. Suppl.  2007;63:445-53.  8)Wang   Z, Widgren EE, Richardson   RT, Orand   MG.  Eppin: a   molecular   strategy   for   male contraception. Soc. Reprod. Fertil. Suppl, 65, 535-42. 
  7.   9)Suri A. (2004). Sperm specific proteins-potential candidate molecules for fertility control. Reprod. Biol. Endocrinol, 2,10.
  8.   10)Chamley   L.W., Clarke G.N. (2007). Antisperm   antibodies   and conception. Semin. Immunopathol, 29(2),169-84. 
  9.   11)Wiley C.A.,  Quinn P.A.  (1984). Enzyme-linked immunosorbent assay for detection of specific antibodies to Ureaplasma urealyticum serotypes. J. Clin. Microbiol, 19(3), 421-6. 
  10.   12)Shi J., Yang Z., Wang M., Cheng G., Li D., Wang Y.,  Zhou Y.,  Liu X., Xu C. (2007). Screening of an antigen target for immunocontraceptives from   cross-reactive   antigens   between   human   sperm   and   Ureaplasma urealyticum. Infect. Immun, 75(4), 2004-11. 
  11.   13)Conforti V.A., De   Avila D.M., Cumming N.S., Wells K.J., Ulker H., Reeves J.J. (2007). The effectiveness of a CpC motif-based adjuvant (CpG ODN 2006) for LHRH immunization. Vaccine, 25(35), 6537-43.
  12.   14)Samuel, A.S., Naz, R.K. (2008). Isolation of human single chain variable fragment antibodies against specific sperm antigens for immunocontraceptive development. Hum. Reprod, 23(6), 1324-37.

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