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At least 199 records · Page 11Linked to original sources
PubMed1992

Contraception.

The principle of vaccination for the purposes of fertility regulation is scientifically elegant and socially compelling. Factors such as economic production, convenience of use, relatively long-lasting but reversible protection, low failure rate and the avoidance of mechanical devices or exogenous hormones make this approach a potentially attractive option for family planning programmes in both developing and developed countries. The major efforts in research and development have involved the prospect of active immunization against specific antigens of sperm, oocyte, zygote and early embryo, and the pregnancy hormone human chorionic gonadotrophin (hCG). Several anti-hCG vaccines have entered clinical trials. They operate by preventing or interrupting pregnancy at the peri-implantation stage probably by neutralizing the luteotrophic effect of hCG. The most refined vaccine is one directed against the unique C-terminal peptide on the beta-subunit of hCG. This vaccine provokes antibodies that are specific for hCG and do not cross-react with human luteinizing hormone (hLH). Preclinical studies in baboons and data from a phase I human trial indicate that this method is free of side-effects and provides the promise of a duration of effectiveness of up to 12 months. Future research will optimize the anti-hCG approach, utilize new vaccine delivery systems and broaden the spectrum of target antigens of potential utility for contraceptive vaccines.

Antigens↗
PubMed1980

Observations on the antigenicity and clinical effects of a candidate antipregnancy vaccine: beta-subunit of human chorionic gonadotropin linked to tetanus toxoid.

Observations on the antibody response and clinical effects of injection of purified beta-subunit of human chorionic gonadotropin covalently linked to tetanous toxoid were made in 15 healthy young women who had previously undergone tubal ligation. Antibodies detectable by radioimmunoassay were found in 14 of the women. Clinical surveillance and immunologic, hematologic, and biochemical tests indicated excellent local and systemic tolerance to the antigen. No significant adverse effects on menstrual function, endocrine status, or health were found.

Antibody Formation↗
PubMed1985

Production of monoclonal antibodies to porcine zona pellucida and their inhibition of sperm penetration through human zona pellucida in vitro.

Two hybridoma cell lines producing murine monoclonal antibodies to antigens common to the zona pellucida (ZP) of pigs and humans were obtained by immunization of mice with solubilized porcine zona antigen. Indirect immunofluorescence tests showed that both these monoclonal antibodies stained the entire layer of porcine ZP but stained different regions of human ZP, one staining the entire layer and the other only the outer surface. At high concentrations, these two monoclonal antibodies directed against antigens common to porcine and human ZP prevented sperm binding and penetration into human ZP in vitro, whereas a monoclonal antibody directed against an antigen restricted to porcine ZP did not have these inhibitory effects. It is concluded that human and porcine ZP share at least two antigens with different locations in the ZP, and that these influence or are essential for interaction of human sperm with the ZP. These results provide a rationale for using porcine ZP clinically as a vaccine for human immunocontraception.

Animals↗
PubMed1994

Immunoregulation of mammalian fertility.

Fertility management is a global issue of agricultural, medical, economic, and social consequence. Although many methods have been devised to both inhibit and assist reproduction, more acceptable alternatives are needed. Regulation by immune intervention is a promising technology as applied to livestock, pets, wildlife, and human beings. Outcome is dictated by site within the reproductive axis that is targeted. Fertility is suppressed by immunization against gonadotropin-releasing hormone, gonadotropins, prostaglandin F2 alpha, oxytocin, gonadotropin receptors, and gamete/embryonic antigens. It also is possible to lyse gonadal cells with ligand-antibody hybrid molecules. Ovulation rates are enhanced by vaccination with inhibin. Antibodies to sex steroid hormones have yielded mixed results. Perhaps recombinant viral vectors can be used to deliver reproductive immunogens. A new and simple technique to generate sustained autoimmune reactions to hormones and cellular antigens entails direct gene transfer into somatic cells. Evolving advances in reproductive immunology and biotechnology should furnish us with novel nonsurgical contraceptives and profertility agents that can be efficiently and safely implemented.

Animals↗
PubMed2005

Characterisation of the antibody response to a totally synthetic immunocontraceptive peptide vaccine based on LHRH.

In this study we describe our attempts to improve the immunogenicity of a synthetic epitope-based vaccine. The vaccine consists of an epitope (P25) that is recognised by CD4+ helper T cells and the target epitope luteinising hormone releasing hormone (LHRH). We show that replacement of the single cysteine residue within P25 with amino acids such as alanine, aminobutyric acid, serine or with carboxymethylated cysteine leads to diminished immunogenicity of the vaccine and only the oxidised dimeric form of the peptide retains the full immunogenicity of the vaccine. Secondly, by measuring the serum antibody response and the number of the antigen secreting cells in spleen and bone marrow we found that three doses of 20 nmol per mouse induced the more consistent and higher immune responses than those induced by three doses of either 2 nmol or 80 nmol per mouse. A greater variation in antibody titre was observed in mice that received the 2 mol or 80 nmol dose regimes. Last, by administering the vaccine in its lipidated form in the presence or absence of additional adjuvant we found that either inoculation regime elicited similar antibody responses. Only at low doses of antigen was a synergistic effect observed when lipopeptide was co-administered with additional adjuvant.

Adjuvants, Immunologic↗
PubMed2006

Effect of porcine zonae pellucidae immunisation on ovarian follicular development and endocrine function in domestic ewes (Ovis aries).

Domestic ewes (Ovis aries) were immunised with porcine zonae pellucidae (pZP) or pZP conjugated to keyhole limpet haemocyanin (KLH) in adjuvant(s) to examine the feasibility of the species to serve as a model for further development of pZP-based vaccines in ungulates. Two immunisation groups were employed, with a third group receiving only adjuvant (n = 5 per group). Early in the study, oestrous activity was monitored by the use of a vasectomised ram fitted with a marking harness. Eventually, ewes were exposed to an intact ram for breeding. In addition, weekly serum and every-other-day faecal samples were collected to measure pZP antibodies and progesterone metabolite concentrations respectively. At the conclusion of the study, fecundity was established, and ovarian tissue was examined. Ewes immunised against pZP : KLH with adjuvant produced minimal antibody absorbance levels, displayed normal oestrous cycles, became pregnant upon introduction of the intact ram and exhibited normal ovarian histopathology. Ewes immunised against pZP with adjuvant produced high antibody absorbance levels, were acyclic following primary immunisation and were infertile. Examination of the ovarian tissue revealed atrophic changes that included: (1) the absence of growing follicles; (2) significant reduction in the number of primordial follicles; and (3) the presence of abnormal granulosa cell clusters lacking oocytes. Antisera displayed immunoreactivity to the major components of pZP, and immunohistochemical labelling of ovarian tissue showed specificity to the ZP. These data are the first generated in an ungulate species showing deleterious effects of pZP immunisation on folliculogenesis and oestrous cyclicity.

Adjuvants, Immunologic↗
PubMed2006

Immunocontraception of Florida feral swine with a single-dose GnRH vaccine.

PROBLEM: Methods to limit fertility of feral swine are needed to reduce transmission of diseases and agricultural and ecosystem damage. Method of Study We evaluated a single-shot GnRH immunocontraceptive vaccine in both male and female feral swine for its effect on fertility and functional status of the reproductive tissues. Captive feral pigs were randomly assigned to receive 1000 or 2000 microg GnRH-KLH vaccine treatments or no treatment. RESULTS: After 36 weeks, none of the 2000-microg-treated females and only 20% of the 1000-microg-treated females were pregnant. This corresponded to reduced serum progesterone, regressed tissues within the reproductive tract and lack of evidence for follicular development leading to ovulation. Males were less responsive to the vaccine than females, but more responsive to the lower dose of the vaccine than the higher dose. CONCLUSIONS: The single-shot GnRH vaccine is effective in controlling fertility of female feral swine and may be useful for population reduction.

Adjuvants, Immunologic↗
PubMed2004

Changes in the reproductive system of male mice immunized with a GnRH-analogue conjugated to mycobacterial hsp70.

Immunosterilization is an attractive alternative to surgical castration. Gonadotropin-releasing hormone (GnRH) controls the production of the gonadotropins thereby having an orchestrating effect on the reproductive hormone cascade and spermatogenesis. Induction of neutralizing antibody can abrogate the effect of the hormone. Current GnRH-based vaccines often require strong adjuvants and/or multiple injections of the vaccines to overcome variability in the response. Heat shock proteins (hsp) have been used as carrier molecules because of their powerful intrinsic ability to enhance an immune response to associated antigens. A GnRH-analogue, GnRH-d6-Lys, was conjugated to recombinant Mycobacterium tuberculosis hsp70. Male BALB/c mice were immunized i.p. with GnRH-hsp70 in the mild adjuvant Ribi or in incomplete Freund's adjuvant (IFA). The initial immunizations were done on pre-pubertal 3-week-old mice, with boosts at 5 and 8 weeks of age. The mice were killed at 10 weeks of age and GnRH-specific antibodies and serum testosterone levels measured. All the immunized mice mounted GnRH-specific antibody responses, with no difference in the mice immunized with GnRH-hsp70/Ribi or with GnRH-hsp70/IFA. There was substantial atrophy of the urogenital complex and significantly (P < 0.0005) reduced levels of testosterone-dependent testicular relaxin-like factor mRNA expression. Mice immunized with GnRH-hsp70/Ribi showed substantially reduced (P < 0.001) serum testosterone levels. These results indicate that hsp70 may serve as a particularly advantageous carrier for GnRH-based vaccines.

Adjuvants, Immunologic↗
PubMed1985

Formulation of a potential antipregnancy vaccine based on the beta-subunit of human chorionic gonadotropin (beta-hCG). II. Use of compounds of the muramyl dipeptide (MDP) family as adjuvants.

Earlier tests of an antipregnancy vaccine consisting of the beta-subunit of human chorionic gonadotropin (beta-hCG) linked by reaction with a carbodiimide reagent to tetanus toxoid (TT) and adsorbed on Al(OH)3 resulted in antibody responses that were judged inadequate in some women. Experiments were therefore conducted to evaluate the effectiveness of additional adjuvants in increasing the antibody response. Muramyl dipeptide (MDP) and several of its analogs were formulated with the vaccine and tested in rabbits. Some of the analogs, and notably N-acetyl-normuramyl-L-alanyl-D-isoglutamine, elicited substantial increments in the ability of the antisera to bind [125I]hCG and in its ability to neutralize hCG in the rat uterine weight assay. The effectiveness of these peptides was greatest when formulated in a water-in-oil emulsion. Increments of 10 fold were attained using a vegetable oil as the oil component. The MDP analogs were much less effective as adjuvants when formulated in oil-in-water emulsions or in aqueous suspensions of the antigen. It is concluded that selected MDP analogs incorporated in a water-in-vegetable oil emulsion can markedly increase the circulating antibody response to the beta-hCG-TT vaccine.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1985

Formulation of a potential antipregnancy vaccine based on the beta-subunit of human chorionic gonadotropin (beta-hCG). III. Evaluation of various vehicles and adjuvants.

Rabbits were used to test the efficacy of several materials as supplementary adjuvants when administered as part of a vaccine formulation consisting of the beta-subunit of human chorionic gonadotropin linked to tetanus toxoid (beta-hCG-TT) and adsorbed on Al(OH)3. In the amounts used, Corynebacterium parvum, levamisole, thymic factor, and N,N-dioctadecyl-N',N'-bis(2-hydroxyethyl)propanediamine exhibited little adjuvant activity although the latter material elicited marginal increments when incorporated in liposomes. A Salmonella lipopolysaccharide preparation (SPLPS) and a streptococcal preparation (OK-432) each gave approximately 7-fold increments in titer. The SPLPS preparation was pyrogenic at the doses used. OK-432 was nonpyrogenic and did not cause other evident undesirable effects. It may therefore prove to be a useful adjuvant. It gave a nearly flat dose response curve over the range of 0.5 to 4.0 mg per rabbit. Incorporation of beta-hCG-TT on Al(OH)3 in a water-in-oil emulsion caused a moderate increase in titers. Incorporation into liposomes or an oil-in-water emulsion was not effective.

Adjuvants, Immunologic↗