New Perspectives immunocontraception

The world’s population is a growing problem of significant magnitude affecting development.  Besides,  unintended pregnancies resulting in elective abortions continue to be a major public health issue. 

In over half of these pregnancies,  women have used some type of contraception but the inconsistent use or the scarce safety of method or intrinsic causes led to conception. It has been widely hoped that immunological methods of fertility regulation by active immunization against specific antigens of the oocyte, sperm, zygote and early embryo,  and the placental pregnancy hormone human chorionic gonadotropin (HCG),  will provide a means to control the problem of world wide population growth.  This idea of vaccine based on HCG immunogens led to several doubts because of its mechanism of action.  In fact, it interfered with the hormone-receptor,  which causes reduction in the function of the corpus luteum and expulsion of the perimplantation blastocyst.  The abortfacient approach on the HCG based contraceptive vaccine limited its applications in many parts of the world(1).
Researchers aim to effect an immune attack on events linked to sperm-ovum contact and fertilization.  Sperm vaccine research is not as advanced as that of ovum vaccine research;  although almost all studies in this field has occurred in animals with varying degrees of success.

However,  research in zona pellucida vaccine development must overcome the risk of immune damage to ovarian oocytes, subsequent development of autoimmune oophoritis, and disturbed ovarian function. The WHO vaccine directed against the C-terminal peptide of beta-HCG induces a specific and safe immune response. The phase 1 trial showed that this vaccine exceeded the threshold of antibody production needed to achieve protection against pregnancy(2).

Contraceptive vaccine(CV)  may provide viable and valuable alternatives that can fulfil most,  if not all,  properties of an ideal contraceptive.  The development of vaccines for contraception is an exciting proposition.  The molecules that are being explored for CV development either target gamete production(gonadotropin releasing hormone,  follicle-stimulating hormone and luteinising hormone), gamete function (zona pellucide (ZP) proteins and   sperm   antigens) or   gamete   outcome   (human   chorionic   gonadotropin (HCG)).

Disadvantages of CVs targeting gamete production are that they affect sex steroids and/or show only a partial effect in reducing fertility. CVs targeting gamete function are better choices.  Vaccines based on ZP proteins are quite efficacious in producing contraceptive effects.  However, they invariably induce oophoritis affecting sex steroids.

Antisperm antibody-mediated immunoinfertility provides a naturally occurring model to indicate how an antisperm vaccine will work in humans. The HCG vaccine is the first vaccine submitted to phase 1 and 2 clinical trials in humans. Sperm constitute the most promising and exciting target for CV(3). Epididymal protease inhibitor (Eppin), a gene on human chromosome 20   expressing   three   mRNAs   encoding, two   isoform   of   a   cystine-rich protein.

Eppin 1 is expressed only in the testis and in the epididymis, Eppin 2 only in the epididymis and,  Eppin 3 only in the testis were also considered in immunocontraception Eppin is one of several serine-protease that are encoded by genes on human chromosome 20.  (4,5).  Recently,researchers have been cloned these epididymal protease inhibitors in human and mice.  Eppin is involved in sperm maturation and fertilization, and the innate immune system of human epididymis.

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