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At least 181 records · Page 10Linked to original sources
PubMed2004

Efficacy of an anti-fertility vaccine based on mammalian gonadotrophin releasing hormone (GnRH-I)--a histological comparison in male animals.

A N-terminal modified gonadotrophin releasing hormone (GnRH-I, tetanus toxoid-CHWSYGLRPG-NH2) conjugate was evaluated histologically in a number of male animal species (mice, dogs and sheep). The immunogen has previously been shown to be highly effective in rats, by suppressing both steroidogenesis and spermatogenesis. However, cross-species efficacy of peptide vaccines is known to be highly variable. Therefore, a comparative evaluation of reproductive tissues from animals immunized against this immunogen adsorbed onto an alum-based adjuvant was made. The sheep and dogs were chosen, as use of anti-fertility vaccines in these species is important in farming and veterinary practice. Changes in testicular size were measured during the immunization period and the greatest alteration (attributed to gonadal atrophy) was observed in the rat. Following euthanasia, the testicular tissue was evaluated for spermatogenesis. The most susceptible species to GnRH-I ablation was the rat, which showed significant (P < 0.0001) arrest in spermatogenesis compared with untreated controls. Testicular sections taken from treated animals were completely devoid of spermatozoa or spermatids, in comparison with 94% of the untreated controls showing evidence of spermatogenesis. The immunized mice and rams also showed significant arrest (P < 0.0001). There was a 30-45% decrease in spermatogenesis and total azoospermia was not apparent. However, the least responsive were the dogs, which showed little significant variation compared to untreated animals and only a 5% decrease in activity. A comparison of the specific IgG response to GnRH-I indicated that in sheep and dogs the response was not maintained, unlike in rodents, suggesting that suppression of fertility may be due to differences in immune responses in different animal species.

Adjuvants, Immunologic↗
PubMed1974

Localization of histocompatibility and organ specific antigens on mouse spermatozoa.

Further studies on the topographic localization of histocompatibility and organ-specific antigens on mouse spermatozoa have been reported. Specific antisera to a histocompatibility antigen (H-2a) and a serum prepared by injecting male mice with syngeneic testicular homogenate were labeled with peroxidase and the antigens were located by immunoelectron microscopy. The organ-specific antigen was located on the sperm head and occasionally on the midpiece, whereas the H-2 antigen was confined to the sperm head. The observations were not quantitative, because of the obvious limitations in the examination of thin sections. The distribution of the 2 antigens may be related to the functions of the various parts of the spermatozoa, although no clear correlation could be suggested. The authors indicate several points of discussion arising from their observations. There is no general agreement at present about the presence or absence of histocompatability antigens on spermatozoa. The reported location of these antigens on spermatozoa conflicts with some earlier results. The present observations must also be considered in relation to the fluid mosaic model of cell membranes, for the localization of antigens to particular sites imples that restrictions are placed on the movement of some membrane constituents.

Biology↗
PubMed2006

Evaluation of two GnRH-I based vaccine formulations on the testes function of entire Suffolk cross ram lambs.

A modified GnRH peptide (CHWSYGLRPG-NH(2)) was conjugated to tetanus toxoid (TT) or diphtheria toxoid (DT) and formulated with Quil A saponin or a sustained release injectible PLGA (poly(lactide-co-glycolide)/triacetin). For the Quil A formulations, two administrations of TT conjugate at 3-weekly intervals were followed by two booster injections with the DT conjugate in entire ram lambs. With the PLGA formulations, only two injections were administered; the first containing TT and the second DT at 6-weekly intervals. Evaluation was carried out by comparing the specific antibody levels produced in relationship to hormone profiles and testicular changes. The Quil A formulation was considered the most effective, as it caused significant reduction in testosterone and follicle stimulating hormone levels, resulting in marked suppression of spermatogenesis.

Adjuvants, Immunologic↗
PubMed1992

Anti-LHRH and anti-pituitary gonadotropin vaccines: their development and clinical applications.

Active immunization against hormones involved in the regulation of reproduction is a promising approach to immunocontraception. The hypothalamic peptide, LHRH, controls the synthesis and release of the pituitary gonadotropins, LH and FSH, which regulate gonadal steroidogenesis, sperm production, follicular development and ovulation. Immunizing female primates against LHRH or LH induces infertility, but also disrupts the menstrual cycle. Immunization against the beta subunit of the placental hormone, chorionic gonadotropin (hCG), or its fragment prevents pregnancy without interfering with menstrual cycles or ovulation. hCG vaccines have reached the stage of clinical trials. FSH and LHRH have been tested for immunocontraception in male primates. While active as well as passive immunization against FSH reduced spermatogenesis severely, azoospermia could not be achieved consistently. Immunization against LHRH effectively suppressed spermatogenesis in rats and rabbits. Normal sexual behaviour was maintained by concomitant androgen administration. Fertility was restored when antibody titres declined and no adverse effects were observed. A number of LHRH vaccine preparations are being tested in men in several countries, including the United States. Since the LHRH vaccine reduces serum testosterone levels the first clinical studies involve men with prostate cancer. These trials will be followed by immunization of normal men if the antibody response is sufficient and no adverse effects are observed.

Animals↗
PubMed1985

Fertility control in the bitch by active immunization with porcine zonae pellucidae: use of different adjuvants and patterns of estradiol and progesterone levels in estrous cycles.

To determine the changes in patterns of 17 beta-estradiol and progesterone levels underlying abnormal cycles in bitches immunized with solubilized crude porcine zonae pellucidae (cPZP), to attempt to circumvent these problems by immunizing with a purified zona fraction (pPZP), and to test the effectiveness of different adjuvants, bitches were immunized with cPZP or pPZP 2-6 times with no adjuvant, Freund's adjuvant, alum adjuvant, or the adjuvant CP-20,961. The bitch immunized without adjuvant had a low titer with a normal cycle and fertility. Immunization with cPZP and adjuvant produced moderate to high titers of antizona antibodies and infertility. Bitches with high titers experienced abnormal estrous cycles. Estradiol rose during proestrus, but instead of falling sharply in early estrus as in controls, it remained elevated. Progesterone did not rise. The moderate-titered bitches had normal cycles and steroid patterns. Bitches immunized with pPZP had moderate titers. Cycles were normal after 3 injections, but after 6 injections one bitch had an abnormal cycle. One pPZP-immunized bitch remained fertile but the others were infertile. Alum was the mildest adjuvant, causing no injection site lesions, but the highest titers occurred with Freund's and CP-20,961 adjuvants. All three adjuvants induced titers sufficient to inhibit fertility. Infertility in bitches immunized with PZP may be due to prevention of zona penetration, because their antisera inhibited zona penetration of oocytes by spermatozoa in vitro. However, alterations in ovarian function preventing ovulation and luteinization could be involved in high-titered bitches.

Adjuvants, Immunologic↗
PubMed1992

Options for immunocontraception and issues to be addressed in the development of birth control vaccines.

Although the number of family planning methods currently available to couples has never been greater, the range and type of options are still not adequate to meet the widely varying personal needs and demands of individuals worldwide. Birth control vaccines offer a number of theoretical attractions although the development, preclinical and clinical testing of such vaccines pose a number of unique problems requiring novel solutions. If the on-going studies in this area are successful, a valuable new family planning method may be available by the end of the current decade.

Animals↗
PubMed1988

Phase I clinical trial of a World Health Organisation birth control vaccine.

A birth control vaccine incorporating a synthetic peptide antigen representing the aminoacid sequence 109-145 of the C-terminal region of the beta subunit of human chorionic gonadotropin (hCG-beta) was submitted to a phase 1 clinical trial. Thirty surgically sterilised female volunteers, divided into five equal groups for different vaccine doses, received two intramuscular injections six weeks apart. Over a six-month follow-up there were no important adverse reactions, and potentially contraceptive levels of antibodies to hCG developed in all subjects. In the highest vaccine dose group, the results gave promise of a contraceptive effect of six months' duration.

Adult↗
PubMed1993

A birth control vaccine is on the horizon for family planning.

Vaccines for control of fertility are likely to have an important impact on family planning methods. They are designed to act by mobilization of an internal physiological process and do not require external medication on a continuous basis. A number of birth control vaccines are at different stages of development, the most advanced being a vaccine inducing antibodies against human chorionic gonadotrophin (hCG). This vaccine consists of a heterospecies dimer (HSD, beta hCG associated with alpha-subunit of ovine luteinizing hormone, beta hCG:alpha oLH) linked to tetanus toxoid (TT) or diphtheria toxoid (DT) as carriers. The vaccine has recently passed an important milestone; it has completed the first leg of phase II efficacy trials. Women of proven fertility leading active sexual life were protected from becoming pregnant at antibody titres > or = 50 ng of hCG bioneutralization capacity per ml. This vaccine has previously been demonstrated to be reversible in its effect. It is free from any notable side-effects on endocrine, cardiovascular and other body functions. Ovulation was not disturbed and menstrual regularity was maintained. A logistic disadvantage of the present vaccine is the requirement for multiple injections. This is expected to be overcome by encapsulation of the requisite doses of the vaccine in biodegradable microspheres, which could be given at a single contact point for sustained antibody titres lasting over a year. A live recombinant vaccine has also been made that elicits high anti-hCG titres in monkeys for nearly 2 years following primary immunization and a booster at 8-9 months.

Adult↗
PubMed1986

Enhancement of antigonadotropin response to the beta-subunit of ovine luteinizing hormone by carrier conjugation and combination with the beta-subunit of human chorionic gonadotropin.

Previous studies have demonstrated the control of fertility in monkeys on immunization with the beta subunit of ovine luteinizing hormone (beta-oLH) along with Freund's complete adjuvant (CFA). An eventual birth control vaccine would demand immunization without CFA. Beta-oLH linked to tetanus toxoid (TT) adsorbed on alum-induced antibody response in bonnet monkeys with detoxified sodium phthalyl derivative of Salmonella enteritidis lipopolysaccharide added only in the first injection. The antibodies reacted with both LH and human chorionic gonadotropin (hCG). A higher immune response was obtained with the use of a conjugate of beta-oLH and beta-hCG linked to a common carrier (TT) or with a mixture of beta-hCG/TT and beta-oLH/TT. In both cases, the antibodies were of high affinity with Ka ranging from 5 X 10(9) to 6 X 10(10) M-1. The antibodies were devoid of reactivity with human thyroid-stimulating hormone and human follicle-stimulating hormone. Monkeys with titers above 120 ng/ml hCG binding capacity (greater than 60 ng/ml in most cases) were protected from becoming pregnant during repeated mating with males of proven fertility in ovulatory cycles.

Animals↗