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Identification of human acrosomal antigen SP-10 in primates and pigs.

The intra-acrosomal human sperm protein SP-10 was previously designated a "primary vaccine candidate" by a World Health Organization Taskforce on Contraceptive Vaccines. In the present study, a monoclonal antibody to SP-10 (MHS-10) was employed on Western blots to identify immunoreactive SP-10 in sperm extracts from baboon (Papio cyanocephalus anubis) and two macaques (Macaca mulatta and Macaca fascicularis). In each of these primates, the MHS-10 monoclonal antibody recognized a polymorphic pattern of immunoreactive peptides similar to that in humans. Immunoreactive SP-10 was also demonstrated in pig sperm. Using purified preparations of the previously described intra-acrosomal molecules acrosin and sperminogen in the pig, we observed that the MHS-10 monoclonal antibody did not react with these proteins, indicating SP-10 is distinct from these known acrosomal components. Sperm from several common species including the rabbit, bull, rat, guinea pig and cat did not immunoreact with the MHS-10 monoclonal antibody. By use of a radioactive probe spanning 628 nucleotides of the open reading frame for SP-10 on Northern blots of poly A + RNA obtained from testes of Macaca fascicularis, Papio papio, and Papio cyanocephalus anubis, a 1.35-kb mRNA of identical size to the mRNA from human testes was identified. These results indicate that baboons, macaques, and pigs may be appropriate models for testing an SP-10-based contraceptive vaccine.

Acrosome↗

Passive immunization against prostatic 'inhibin' peptide as a male contraceptive.

Passive immunization of adult male hamsters for 12 weeks against peptide (As-PIP), a sperm coating antigen, resulted in selective elevation of the blood levels of FSH, impairment of spermatogenesis, and complete infertility when males were mated with normal cycling females. Passive immunization of male marmosets with As-PIP for 8 weeks was also effective and was reversible, without causing any obvious change in mating behaviour. These preliminary studies in hamsters and marmosets indicate that antibodies to a prostatic 'inhibin' peptide represent a promising new approach to male contraception.

Animals↗

Vaccination for contraception.

Vaccination for birth control has several advantages over currently available methods of family planning and should prove an attractive addition to the contraceptive armamentarium both in developing countries and in a developed country such as Australia. Concerns have been voiced by consumer health advocates that vaccines, like other long acting contraceptive methods, may be abused by health authorities in developing countries and by their use in vulnerable groups such as aborigines in our own country. These concerns need to be recognised and addressed. More difficult to accommodate are the anxieties expressed by feminist groups about the 'loss of control' and 'lack of body awareness' inherent in a method, such as a vaccine, that is relatively easily administered and has no overt side effects. There is no evidence that these concerns are shared by women in general. The antifertility vaccine that will most likely be applied first in family planning programmes is one directed against the pregnancy hormone hCG. A WHO vaccine directed against the C-terminal peptide of beta-hCG provokes a specific and safe immune response and will enter Phase 2 trials in Sweden this year. Subsequent developments with this vaccine will include the replacement of the current emulsion vehicle by a delivery system based on biodegradeable microspheres which will give a more sustained antigen release and duration of effectiveness.

Antigens↗

Immunocontraceptive efficacy of synthetic peptides corresponding to major antigenic determinants of chicken riboflavin carrier protein in the female rats.

PROBLEM: Earlier studies have demonstrated that antibodies directed towards the N-terminal (residues 10-17) and C-terminal (residues 200-207) regions on chicken riboflavin carrier protein (RCP; 219 AA) are effective in pregnancy termination in rodents and sub-human primates. In the present study, the immunocontraceptive potential of three additional immunodominant sequences comprising of residues 33-49, 64 83 and 130-147 (CYA, CED and CGE peptides, respectively) of chicken RCP was investigated. METHOD OF STUDY: The three antigenic peptides were synthesized by using Fmoc chemistry. Oligoclonal antibodies were generated in rabbits. Bioneutralizing capacity of these peptides was assessed by passive and active immunoneutralization studies. RESULTS: All the three peptides-specific antisera recognized their cognate epitopes on native RCP. When the affinity purified peptide IgG were administered on three consecutive days to pregnant rats (on days 10, 11 and 12), it was observed that the rats injected with CED and CGE-IgG failed to deliver any pups whereas the animals which received CYA IgG delivered normal pups. Active immunization of fertile female rats with CED or CGE peptide conferred protection from pregnancy. CONCLUSIONS: These results demonstrate the presence of two additional stretches in chicken RCP which can serve as mini-vaccines.

Amino Acid Sequence↗

Immunology and reproduction. I. Sterility immunology.

This review on sterility immunology deals exclusively with immunological mechanisms hindering gamete junction. It does not elaborate the different immunological aspects of infertility after gamete junction. Thus spermatozoal seminal plasma and ovum antigens producing auto- or isoimmunization as immunological mechanisms hindering gamete junction in vitro and in vivo are discussed. Local immune response is compared to general immune response discerning between antibody production and cellular immunity. The commonly used diagnostic tools, the application of these test methods, the clinical therapeutical significance and the scientific objectives for further research in the area of reproductive immunology are outlined. It becomes evident that research in immunology of reproduction is performed with two targets: (1) diagnosis and treatment of the so-called 'immunological sterility', and (2) development of an immunological contraceptive.

Animals↗

Overview of advances in contraception.

For most of man's existence, natural checks on fertility ensured that the numbers of the population more or less matched the resources available. It is only in the last few generations that man has so dominated the natural environment that the numbers of people in the world have increased exponentially, unchecked by natural disasters such as disease and starvation. Coincidental with extended life expectancy, the fertility rate of individual women has increased with the advent of bottle feeding and the decline in the contraceptive effects of breast feeding. Contraception has become increasingly important to individuals, allowing them to break free from the 'burden of excessive fertility'.

Angiogenesis Inhibitors↗

[Immunocontraceptive effect of a synthetic chimeric peptide of sperm].

OBJECTIVE: To investigate the immunocontraceptive ability of a new synthetic chimeric peptide with 35 amino acid residues. METHODS: A chimeric peptide with 35 amino acid residues was synthesized based on the amino acid sequence of SP17, a protein specific to murine testis/sperm, and cyritestin. The purified product, with keyhole limpet hemocyanin (KLH), was injected subcutaneously into the pad of female and male Balh/C mice. Blood was extracted from the ophthalmic arteries of the mice to identify the corresponding proteins from organs of mice and/or rat and human being by Western blotting. The chimeric peptide was injected into other female mice that were then raised together with male mice in the same cages to observe their status of pregnancy. Freund' adjuvant or normal saline were injected into the controls. RESULTS: The purity of the new chemiric peptide was 95%. The highest specific IgG titre in mouse serum was 1:6000 and the highest titre of specific IgA in the washing of vaginal mucous membrane of female mice was 1:300. The specific antiserum from the mice immunized by the chimeric peptide and KLH could identify two proteins with the molecular weights of 22 000 and 55 000 from testes of mice, rats, and human being. Western blotting showed no band for the extracts of mouse liver, spleen, and kidney. The pregnancy rate of female immunized mice was 61.11%, significantly lower that those in the controls (P < 0.05). The average number of cubs in a litter was less in the experimental group than in the controls (P < 0.05). CONCLUSION: The new chimeric peptide with 35 amino acid residues stimulates powerfully humoral and mucous immunity in mice and obviously decreases the pregnancy rate and the number of cubs in each litter in mice.

Animals↗

A search for immunocontraceptive agent from marine sources--role of antispermatheca globulin of Telescopium telescopium on fertility regulation in male rat.

Polyclonal antisera were developed in rabbits against 'spermatheca', the reproductive gland of T. telescopium, a marine mollusc. The gland contains spermatozoa. Antisera and its IgG fraction (ASTG) indicated common antigenic determinants by immunodiffusion and had titer values 81920 and 1280 against crude antigen extract. Cycling female rats when exposed to passively immunized male rats with different doses of ASTG, had reduction in implantation sites and litter size. Females had pseudopregnancy when exposed to higher doses of immunized males and had normal cycle after 20 days in average. ASTG in male rats caused decrease in weight of the reproductive glands, alteration in sperm concentration, motility and morphology, formation of multinucleated giant cells and vacuoles leading to arrest of spermatogenesis and reduction in seminiferous tubular diameter. The effects were dose dependent with reversible infertility. The results indicate presence of a common antigenic determinants which cross-react with vertebrates and existence of common relation through phylogenetic evolution and their immune responses.

Animals↗

Vaxstrate: an anti-reproductive vaccine for cattle.

This paper describes the development of a vaccine for the prevention of pregnancy in female cattle. The vaccine is based on the established principle that antibodies to the hypothalamic releasing hormone, gonadotrophin releasing hormone (GnRH) block the action of GnRH on pituitary secretion of luteinizing hormone and follicle stimulating hormone, leading to gonadal atrophy in mammals. The vaccine comprises an immunogenic GnRH:ovalbumin conjugate formulated in a novel double adjuvant system and is administered in a two-dose treatment regimen. Field trials have confirmed efficacy and the product, Vaxstrate, has now been registered and commercialized.

Animals↗