Review Article ANTI-SPERM CONTRACEPTIVE VACCINES: A HYPOTHESIS TO DEVISE A NEW, INNOVATIVE CONTRACEPTIVE AGAINST SPERMS INSIDE A WOMAN’S UTERUS SUBATHRADEVI C * , TANYA JAIN, TANMAYEE HAZARIKA, ANTIKA SINHA, SOMI ALI, SHUBHADA NEMANI, MOHANASRINIVASAN V School of Bio sciences and Technology, VIT University, Vellore 632014, Tamil Nadu, India. *Email: subaresearch@rediffmail.com Received: 23 Sep 2013, Revised and Accepted: 15 Oct 2013 ABSTRACT This article states a hypothesis of devising a new, immune-contraceptive vaccine against sperms. Experimental research has already been carried out in this area, using antigens from the sperm head. This poses several problems like acrosomal interference and variations caused due to capacitation of the sperm. We have suggested that the SPAG6 antigen on the sperm tail be used for the same purpose, which will overcome all such troubles and maintain a uniformity of interaction in the recipient female. This vaccine, when formulated, can be used to immunize females who use a convenient and non-invasive birth-control method. Keywords: Sperm, Immune-contraceptive, Vaccine, Birth control, SPAG6, Infertility. INTRODUCTION The fast population growth in many countries has been a major problem; therefore, the family planning program needs to be implemented widely and effectively. The human population continues to grow and is estimated to rise to 10.1 billion by the end of the century. [1]. There is a need for safe and highly effective contraceptive options for both men and women. Until recently, male contraception was always associated with the problems of low efficiency, irreversibility and unwanted side effects.[2] Development of tools or materials for contraception is still underway; one of them is the immune-contraception method.[3,4] The aim of this hypothesis was to design an immune –contraceptive vaccine using SPAG 6 protein. Anti-sperm antibodies (ASA) are a reason of infertility in some males. ASA impair both sperm function and fertilization. These auto antibodies may affect pre as well as post-fertilization stages of the reproductive process [5]. Mutations in the SPAG6 gene could be one cause for male infertility.[6] Sperm-associated antigen six is a protein that is encoded by the SPAG6 gene in human males. This protein is present in the tail of permeabilized human sperm and is involved in flagellar motility and maintenance of the structural integrity. The protein is recognized by ASA from an infertile man. The correlation of ASA with cases of unexplained infertility implicates a role for these antibodies in blocking fertilization [7].Working along these lines; we can develop antibodies against human sperm in vitro. We have hypothesized that monoclonal antibodies (MoAb) against human ejaculated sperm can be developed from mice immunized with sperm membrane preparations. The tissue and species specificity of MoAb against SPAG6 can be evaluated using antibody preparations with heterologous sperm and seminal plasma. Vaccination with these sperm antigens will cause a reversible contraceptive effect in females and males, by inducing a systemic and local antisperm antibody response. Infertility after anti-sperm antibody binding can be caused by auto agglutination, sperm cyto-toxicity, blockage of sperm-ovum interaction, and inadequate motility. The efficacy can be enhanced by combination vaccination, including peptides based on various sperm antigens, like using multi-epitope vaccines combining sperm proteins involved in various steps of the fertilization cascade [8]. Contraceptives In the present day, birth control and family planning are of major concern. However, the contraceptive options available to men are limited to vasectomy, condoms, and early withdrawal, all of which present certain problems. The former is considered to be a permanent method of birth control, considering that the surgery to reverse infertility has only a limited success rate. The latter two methods have failure rates even under perfect use. They are between 80 and 90% successful under actual use. Therefore, it is necessary to develop new male contraceptives that are safe, reversible, and more effective than current offerings. Contraceptive vaccines may be an attractive addition to the currently available range of family planning methods, offering several potential advantages [9]. Several antigens of gametogenic origin have already been identified and successfully applied to induce infertility in experimental animals. Contraceptive Vaccines An examination of the literature covering, the last decade has shown that there are a diverse number of immuno- contraceptive vaccines (CV) that are still under research and development. Current Contraceptive vaccines target gamete production [luteinizing hormone-releasing hormone (LHRH ⁄GnRH), follicle stimulating hormone (FSH)], gamete function [sperm antigens and oocyte zona pellucida (ZP)] and gamete outcome [human chorionic gonadotropin (HCG)]. Vaccines targeting gamete production affect hormone production. Vaccines inhibiting gamete function are the preferred target. Although CV targeting ZP has a high contraceptive efficacy, they cause oophoritis, affecting sex hormones. For human applicability, the current research is focused on isolating infertility- related epitopes (B-cell epitopes), and modulation of immunogenicity by various carriers and adjuvants. The HCG vaccine, which targets gamete outcome, is the first CV that has undergone Phase I and Phase II clinical trials in humans [8]. Spermatozoa have drawn much attention for CV development. During the last two decades, significant progress has been made in the field of anti-sperm immune-contraception. Several sperm antigens have been delineated, cloned, and sequenced that have function in sperm physiology and fertilization. A series of monoclonal antibodies (MCAs) have been generated that inhibit fertility in various species of animals. A few of the sperm antigens recognized by these MCAs are sperm-specific and have been isolated and biochemically and immunologically characterized. Notable among these are lactate dehydrogenase (LDH)-C4, rabbit sperm auto antigens (RSAs), PH-20, SP-10, HSA-63, fertilization antigen-1(FA-1), FA-2 and cleavage signal-1 (CS-1) protein [10]. These are antigens present on the sperm head, and this approach is limited by the fact that the acrosomal membrane of the sperm head undergoes changes during maturation, or after ejaculation and just before fertilization. Method to develop a contraceptive vaccine- A hypothetical approach Sperms are motile structures that contain an outer membrane. The whole sperm cannot be used for the CV development as it has International Journal of Pharmacy and Pharmaceutical Sciences ISSN- 0975-1491 Vol 5, Suppl 4, 2013 A A c c a a d d e e m mi i c c S S c c i i e e n n c c e e s s