The ideal goal of male immunocontraception is to develop a safe, effective, convenient, acceptable and reversible contraceptive vaccine. Current studies mainly focus on screening the most suitable target antigens from reproductive hormones and sperm functional proteins for the development of immuno contraceptive vaccines. The vaccine targeting reproductive hormones has not been widely used due to its different degrees of side effects and complicated operation. Recent studies show the practicability and applicability of the immuno contraceptive vaccine targeting sperm specific antigens, but its development is confronted with many challenges, such as how to select appropriate target antigens, how to enhance the immunogenicity of the vaccine, how to choose appropriate drug-delivery ways, how to reduce its side effects, and how to decrease its cost.
Antigens ; immunology ; Contraception, Immunologic ; methods ; Contraceptive Agents, Male ; immunology ; Humans ; Male ; Vaccines ; immunology

A series of sperm membrane antigens, the important molecular markers associated with the program of spermatogenesis and maturation of sperm, which also are for attachment of the physiological mechanism of the sperm-egg interaction and fusion and the pathological changes in the infertility, were reviewed. Some traditional crucial sperm membrane proteins, such as FA-1, PH-20, fertilin, have been cloned and sequenced, and some novel gene which encode new proteins associated with the sperm membrane also have been screened out successively. All of these provided a basement for lucubration of these proteins and the research of the contraception vaccine.
Animals ; Antigens, Surface ; genetics ; immunology ; Cell Membrane ; immunology ; Cloning, Molecular ; Humans ; Male ; Mice ; Spermatozoa ; immunology ; Vaccines, Contraceptive

Lactate dehydrogenase-C4 isozyme has been widely studied as the sperm-specific antigen in the research of the contraceptive vaccine. Developmental and testis-specific expression of the LDH-C gene requires mechanisms for activation in germ cells and repression in somatic cells. LDH-C promoter, several transcription factors and methylation of CpG dinucleotides have been proved of governing action on LDH-C gene transcription. The strategy is to induce antibodies in the female reproductive tract against LDH-C antigens at a sufficient level to block fertilization. Chemically modified LDH-C4 offers a potential application in the induction of infertility of homologous species in marked contrast to native LDH-C4. In addition, advances are being made in researches on the male contraceptive vaccine and synthetic peptide immunocontraceptive.
Animals ; Humans ; Isoenzymes ; genetics ; immunology ; L-Lactate Dehydrogenase ; genetics ; immunology ; Male ; Mice ; Papio ; Rabbits ; Spermatozoa ; enzymology ; Transcription, Genetic ; Vaccines, Contraceptive ; immunology

The epididymal protease inhibitor (Eppin) abounds in human semen and on the surface of human spermatozoa, specifically produced by the testis and epididymis. Recombinant Eppin has effected infertility in the immunized monkey and promises to be an effective vaccine for human immunocontraception. This article reviews the advances in the studies of Eppin gene and protein construction and its molecular mechanism of causing immunologic infertility and regulating PSA hydrolysis of Semenogelin.
Animals ; Humans ; Infertility, Male ; immunology ; Male ; Mice ; Primates ; Proteinase Inhibitory Proteins, Secretory ; chemistry ; genetics ; immunology ; physiology ; Seminal Vesicle Secretory Proteins ; physiology ; Vaccines, Contraceptive

Mammalian zona pellucida 3(ZP3) plays an important role in the induction of capacitating sperm acrosome reaction. In this study, we obtained the soluble mZP3 fusion protein and identified its immunoreactivity. mZP3 cDNA was cloned into plasmid pMAL-p2x, and the recombinant plasmid was transformed into Escherichia coli BL21. To get the soluble mZP3 fusion protein, we tried to optimize the expression conditions, including additives, IPTG concentrations, temperatures and induction duration. Then, Western blotting and ELISA were used to identify the immunoreactivity of the purified protein. Based on the optimization experiments, we concluded that the best soluble expression conditions for the mZP3 fusion protein involved incubation to an A600 of 0.6, addition of glucose to a final concentration of 0.02 mol/L, addition of IPTG to a final concentration of 0.6 mmol/L and then further incubation for 4 h at 25 degrees C. Western blotting and ELISA showed that the mZP3 fusion protein retained immunoreactivity. The fusion protein can be used as solubility antigens for developing the immunocontraception vaccines of mZP3 and detecting the immune effects of the vaccine.
Animals ; Egg Proteins ; biosynthesis ; genetics ; immunology ; Escherichia coli ; genetics ; metabolism ; Female ; Membrane Glycoproteins ; biosynthesis ; genetics ; immunology ; Mice ; Receptors, Cell Surface ; biosynthesis ; genetics ; immunology ; Recombinant Fusion Proteins ; biosynthesis ; genetics ; immunology ; Solubility ; Vaccines, Contraceptive ; immunology ; Zona Pellucida Glycoproteins

Immunocastration is a considerable alternative to a surgical castration method especially in male animal species for alleviating unwanted male behaviors and characteristics. Induction of high titer of antibody specific for gonadotropin-releasing hormone (GnRH) correlates with the regression of testes. Fusion proteins composed of canine GnRH and T helper (Th) cell epitope p35 originated from canine distemper virus (CDV) F protein and goat rotavirus VP6 protein were produced in E. coli. When these fusion proteins were injected to male dogs which were previously immunized with CDV vaccine, the fusion protein of GnRH-CDV Th cell epitope p35 induced much higher antibody than that of GnRH-rotavirus VP6 protein or GnRH alone. The degeneration of spermatogenesis was also verified in the male dogs immunized with the fusion protein of GnRH-CDV Th cell epitope p35. These results indicate that canine GnRH conjugated to CDV Th cell epitope p35 acted as a strong immunogen and the antibody to GnRH specifically neutralized GnRH in the testes. This study also implies a potential application of GnRH-based vaccines for immunocastration of male pets.
Amino Acid Sequence ; Animals ; Antibodies/blood ; Base Sequence ; Contraception, Immunologic/methods/*veterinary ; Distemper Virus, Canine/*immunology ; Dogs/immunology/*physiology ; Epitopes, T-Lymphocyte/*immunology ; Fertility/immunology ; Gonadotropin-Releasing Hormone/chemistry/*immunology ; Male ; Molecular Sequence Data ; Organ Size ; Recombinant Proteins/immunology ; Spermatogenesis/immunology ; T-Lymphocytes, Helper-Inducer/immunology ; Testis/immunology ; Vaccines, Contraceptive/immunology

To study whether the antibody against the testis form of the nuclear autoantigenic sperm protein (tNASP) could result in reproductive failure, we successfully cloned and expressed a 339-bp cDNA fragment of mouse tNASP (mtNASP). Using mouse as a model, recombinant mtNASP (rmtNASP) and a synthetic peptide, human tNASP(393-408) (htNASP(393-408)), were investigated for their antifertility effect. Active immunization with rmtNASP or the synthesized peptide raised high antibody titers in the immunized mice. Sperm-egg binding and fusion assay were carried out in 8-10-week-old BALB/c mice. Sperm-egg binding and in vitro fertilization of mouse oocytes were inhibited by co-incubation of zona-free mouse oocytes with capacitated mouse spermatozoa in the presence of varying concentrations of the antisera against rmtNASP. There was a significant antifertility effect in animals immunized with rmtNASP or the synthesized peptide. The effect on fertility in the mice immunized with the synthesized peptide was reversible. Our data indicate that active immunization with rmtNASP antigen may induce a strong antibody response that causes an inhibition of fertility.
Adult ; Animals ; Autoantibodies ; administration & dosage ; immunology ; Autoantigens ; chemistry ; immunology ; pharmacology ; Contraception, Immunologic ; Female ; Fertility ; drug effects ; immunology ; Humans ; Immune Sera ; immunology ; pharmacology ; Male ; Mice ; Nuclear Proteins ; chemistry ; immunology ; pharmacology ; Rabbits ; Recombinant Proteins ; immunology ; Sequence Analysis, Protein ; Sperm Motility ; drug effects ; immunology ; Sperm-Ovum Interactions ; immunology ; Spermatozoa ; drug effects ; immunology ; Vaccines, Contraceptive ; immunology ; pharmacology