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

Sperm protein 17 (Sp17) is a testis-specific protein involved in acrosome reaction in spermatozoa. However, the Sp17 gene has been recently detected in normal non-testis tissues and malignant neoplasias. Therefore Sp17 may be a potential target for immunocontraception and a suitable target for tumor immunotherapy. This paper reviews the advances in the protein characterization, expression and distribution, and biological function of Sp17 and its clinical research.
Animals ; Antigens, Surface ; Carrier Proteins ; analysis ; physiology ; Contraception, Immunologic ; Humans ; Immunotherapy ; Male

The epididymal protease inhibitor (Eppin) has recently been cloned in human and mice, which is specifically expressed in the epididymis and testis. Eppin is a cystine-rich secretory protein which contains signal peptide, WAP and BPTI motifs. Eppin is involved in sperm maturation and fertilization, and in the innate immune system of human epididymis. Immunocontraception with Eppin is effective and reliable, but its safety is to be further proved. This paper summarizes the effects of Eppin of fertilization and immunity, as well as its utilization in immunocontraception.
Animals ; Contraception, Immunologic ; Epididymis ; immunology ; Fertility ; physiology ; Haplorhini ; Male ; Mice ; Proteins ; immunology ; physiology ; Spermatozoa ; physiology

Surgical castration performed to reduce male-associated problems results in pain and microbial infections in male animals. Therefore, immunocontraception, which is mediated by the animal's own antibodies against reproductive hormones, has been recommended as an alternative to surgical castration when considering the animal's welfare. In this study, a new immunocontraceptive vaccine composed of six tandem copies of gonadotropin-releasing hormone (GnRH) fused to rat granulocyte-macrophage colony-stimulating factor (GM-CSF) was developed, and its efficacy was evaluated in male rats. Three different doses (10, 50, and 100 µg) of recombinant GM-CSF–GnRH protein were injected three times at intervals of two weeks into male rats. The rats vaccinated with three doses of GM-CSF–GnRH produced a significantly higher level of antibodies against GnRH than that in the negative control rats. Severe atrophy of gonads was observed in rats vaccinated with three doses of GM-CSF–GnRH but not in the negative control rats. The results reveal that the new GnRH vaccine conjugated with rat GM-CSF induces efficient immunocontraception in male rats. This formulation of the immunocontraceptive vaccine would be applicable to both domestic and pet male animals.
Animals ; Antibodies ; Atrophy ; Castration ; Contraception, Immunologic ; Gonadotropin-Releasing Hormone* ; Gonads ; Granulocyte-Macrophage Colony-Stimulating Factor* ; Humans ; Male* ; Rats* ; Vaccines

Fertilin beta plays an important role in fertilization by its disintegrin domain as a sperm-specific antigen. This paper reviews its structure, localization and roles in fertilization, and suggests that fertilin beta, as an important target antigen, has a very promising value in the development of human immunocontraceptive vaccine.
ADAM Proteins ; Animals ; Contraception, Immunologic ; Fertilins ; Fertilization ; Humans ; Male ; Membrane Glycoproteins ; chemistry ; genetics ; physiology ; Metalloendopeptidases ; chemistry ; genetics ; physiology ; Vaccines ; immunology

OBJECTIVETo test anti-Sp17 antibodies in the serum of AsAb positive infertile patients, to investigate the proportion of anti-Spl7 antibodies in AsAb and their potential application to the serologic diagnosis of immune infertility and immunocontraception.

METHODSWith human recombinant Sp17 as the antigen, the ELISA method was used to detect the positive rate, antibody titre and content of anti-Sp17 antibodies in the AsAb positive serum.

RESULTSThe positive rate of anti-Sp17 antibodies in the AsAb positive serum was 56.5%, with no significant difference in the gender aspect. The percentage of anti-Sp17 antibodies in AsAb was (10.09 +/-7.45) %, with statistical significance (P <0.05).

CONCLUSIONSp17 is an important sperm antigen. Anti-Sp17 antibodies in the serum can be taken as auxiliary diagnostic index of infertility, and Sp17 is shown to be a potential candidate immunocontraception vaccine.

Adult ; Antigens, Surface ; immunology ; Autoantibodies ; blood ; Carrier Proteins ; immunology ; Contraception, Immunologic ; Female ; Humans ; Infertility, Male ; blood ; immunology ; Male ; Spermatozoa ; immunology

Gonadotropin-releasing hormone (GnRH) is secreted from the hypothalamus and anti-GnRH antibodies are not formed under normal conditions. However, administration an excess of recombinant GnRH protein results in the formation of anti-GnRH. We evaluated the efficacy of the recombinant Salmonella typhimurium flagellin fljB (STF2)-GnRH vaccine in inducing infertility in 17 intact male cats. The first vaccination and a boosting vaccine was injected for examination. Serum was obtained from blood collected at monthly intervals and anti-GnRH antibodies and testosterone concentrations were determined. Six months after the vaccination, testicular samples are obtained and used for histological examination. Compared with sham control group, the injection groups showed an increase in anti-GnRH antibody titers and testosterone concentrations tended to be reduced in the injection groups and increased in the control group. Histological evaluations and Johnsen's testicular biopsy scores revealed testicular hypoplasia in the 2 injection groups. Consequently, normal sexual maturation with sperm production was observed in the control group. In contrast, the cats that received the GnRH vaccine showed weak (2 of 7 cats) or moderate (4 out of 7 cats) dose-dependent infertility effects. On the basis of the results, the STF2-GnRH vaccine was identified to be effective in inducing infertility in male cats. The results of this study thus indicate the possibility of immunological castration targeting feral cats.
Animals ; Antibodies ; Biopsy ; Castration ; Cats ; Contraception, Immunologic ; Fertility Agents ; Flagellin ; Gonadotropin-Releasing Hormone ; Humans ; Hypothalamus ; Infertility ; Male ; Salmonella typhimurium ; Sexual Maturation ; Spermatozoa ; Testis ; Testosterone ; Vaccination ; Vaccines

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