PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Contraception, Immunologic”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 523 records · Page 29Linked to original sources
PubMed1996

The potential of the zona pellucida as a target for immunocontraception.

PROBLEM: To investigate the contraceptive potential of the zona pellucida. METHOD: Generation of antibodies against native and recombinant zona glycoproteins which have then been assessed for their capacity to disrupt sperm-zona interaction in vivo and in vitro. The animal model selected for these studies was the common marmoset and the end points examined were antibody titre, ovarian cyclicity and fertility. RESULTS: The fact that antibodies against the major zona glycoprotein, ZP3, block both the primary and secondary phases of sperm-zona interaction suggests that this molecule might have potential for contraceptive vaccine development. Active immunization of marmoset monkeys with native porcine ZP3 or recombinant human ZP3 produced long term infertility but also precipitated a premature decline in the primordial follicle population. CONCLUSIONS: Future studies will have to determine whether a safe, effective vaccine can be engineered by coupling unique B-cell epitopes from ZP3 to foreign T-cell antigens.

Animals↗
PubMed1996

ZP3 peptide vaccine that induces antibody and reversible infertility without autoimmune oophoritis.

Autoantibodies to ZP3, a major glycoprotein of the zona pellucida (ZP) with sperm receptor function, can block sperm/oocyte interaction. However, only mice of certain major histocompatibility complex (MHC) haplotype respond to the ZP3 peptide. Moreover, ZP3-specific T cells can mediate ovarian autoimmune disease. A chimeric peptide has been designed that induces antibody to native ZP3 regardless of the MHC haplotype of the inbred mice tested. This results in reduction in fertility that is reversible. Infertility correlates well with ZP antibody titer, and the mice do not develop concomitant autoimmune oophoritis. The vaccine contains (1) a promiscuous foreign T-cell peptide capable of eliciting a T-cell response regardless of the animals' MHC haplotype, and (2) a modified native B-cell peptide of ZP3.

Animals↗
PubMed1996

Update on the Center for Recombinant Gamete Contraceptive Vaccinogens.

The overall goal of the Center for Recombinant Gamete Contraceptive Vaccinogens is to develop a contraceptive vaccine which will induce antibodies in the female reproductive tract at sufficient levels to block fertilization. It is envisioned that antibodies developed by this vaccine will act to agglutinate, immobilize or coat either the egg or the sperm in the oviduct, uterus, cervix or vagina. Thus, the vaccine will exert its effects before the fertilization event, as a "prefertilization contraceptive." The Center has focused its activities over the past 4 years on four areas: 1) sperm antigens: the identification and characterization of novel sperm surface molecules which are attractive candidates for inclusion in a vaccine; 2) zona antigens: the identification of synthetic peptides derived from the zona pellucida which possess contraceptive potential without adverse pathology; 3) oral vaccine delivery: the development of live Salmonella vectors which deliver vaccine antigens through the oral route and which will stimulate secretory immunity in the female reproductive tract; and 4) animal testing: the testing of vaccine formulations in in vitro fertilization models, in small animals, in monkeys and in baboons. In addition, preparations for human testing are underway through preparation of an Investigational New Drug Application to begin Phase I human trials of a LDH-C4 peptide vaccine.

Animals↗
PubMed1996

Luminal and glandular endometrial epithelium express integrins differentially throughout the menstrual cycle: implications for implantation, contraception, and infertility.

PROBLEM: Integrins belong to a family of cell adhesion molecules that are present on virtually all cells. The temporal and spatial expression of these important proteins on the human endometrium suggests that certain integrins may participate in the cascade of molecular events leading to successful implantation. METHODS: Using immunohistochemistry, we studied the expression of 12 different integrins in up to 600 samples of human endometrium throughout the menstrual cycle. Intensity and distribution of staining was determined using the semiquantitative HSCORE, with specific focus on the differences between glandular and luminal expression. RESULTS: We noted that the glandular and luminal epithelium undergo independent alterations in integrin expression throughout the menstrual cycle. Specifically, glandular epithelium express certain integrins only during the window of implantation, while luminal epithelium down-regulate certain integrins during this time. The expression of one integrin (the alpha v beta 3 vitronectin receptor) on both luminal and glandular epithelium coincides with the time of embryo attachment; aberrant expression of this integrin is associated with infertility. CONCLUSION: It appears that the endometrium is a unique tissue with regard to the number of integrins that undergo temporal and spatial changes during the menstrual cycle. These data may offer new directions for the development of a novel contraceptive approach targeted to the endometrium as well as a better understanding of occult causes of infertility in women.

Contraception, Immunologic↗
PubMed1996

Identification of human sperm antigen recognized by serum of an immunoinfertile woman: a candidate for immunocontraception.

PROBLEM: It has been well documented that antisperm antibodies can be causative factors of infertility. In this study we have identified an antigen on human sperm surface using serum of an immunoinfertile woman; it is thus a candidate for immunocontraception. METHOD: Thirty-three women of reproductive age who were infertile were screened for presence of antisperm antibodies by indirect immunofluorescence and agglutination assay. The serum of one such woman, SU-4, reacted with her husband's as well as normal donor sperm and recognized a band of apparent molecular weight of 71-kDa on Western blot. Anti-71-kDa antiserum was raised in rabbit by eluting 71-kDa protein and was characterized by agglutination test, immunofluorescence assay, transmission electron microscopy, flow cytometry, and sperm-egg interaction in mouse system. RESULTS: Interestingly, sera raised in rabbit against 71-kDa antigen, was identified by immunoinfertile serum of SU-4, revealed similar results of localization of human acrosome. Anti-71-kDa antibodies showed cross-reactivity with other species of sperm, demonstrated inhibition of sperm attachment to oocytes in an in vitro mouse system, and revealed surface binding of human live sperm by flow cytometry. Transmission electron microscopy documented the presence of 71-kDa antigen in the acrosomal compartment. CONCLUSION: This study has put in evidence an antigen of apparent molecular weight of 71-kDa in all donor sperm tested in this study. The presence of this antigen on the sperm of several species will enable us to determine the efficacy of this antigen in controlling fertility in vivo in both rodents and primates. This antigen may be a candidate for immunocontraception.

Adult↗
PubMed1997

The HSD-hCG vaccine prevents pregnancy in women: feasibility study of a reversible safe contraceptive vaccine.

PROBLEM: To develop a vaccine for reversible control of fertility in women. MATERIALS AND PROTOCOLS: Purified beta subunit of hCG annealed to purified alpha subunit of ovine LH linked chemically to tetanus toxoid (TT) and diphtheria (DT); vaccine employed at 300 micrograms gonadotropin equivalent per injection adsorbed on alhydrogel with 1 mg SPLPS added in the first injection; Phase I safety trials in 47 women with elective tubal ligation; Phase II efficacy studies in 148 proven fertile women (2 children), sexually active, desirous of family planning using IUD; IUD removed when anti-hCG titres exceed 50 ng/ml hCG bioneutralization capacity; boosters given to maintain above threshold antibody levels; post coital tests conducted in 8 volunteers; sera of protected women analysed for immuno-determinants recognized by competitive enzyme immunoassays employing a panel of monoclonal antibodies and by direct binding to synthetic peptides; recombinant vaccines expressing beta hCG as a secreted product or as a fused protein anchored on membrane. RESULTS: Immunization was well tolerated with no significant changes in endocrine, metabolic and hematological indices. Normal ovulatory cycles were maintained as indicated by menstrual regulation. The vaccine was highly effective in preventing pregnancy (1 pregnancy in 1224 cycles ) at and above antibody titres of 50 ng/ml. Antibodies declined in course of time in absence of boosters, with conceptions occurring below 35 ng/ml titres indicating regain of fertility. Ability of antibodies to prevent pregnancy was confirmed by post coital tests. High avidity (10(10) M-1) and other characteristics of antibodies generated by the vaccine are described and compared with those induced by two other hCG vaccines having undergone Phase I trials. The antibody response of the HSD vaccine in humans is characterized predominantly to an epitope recognized by the monoclonals 206 and P3W80. The antibodies had low or no reactivity with the carboxy terminal peptide and 38-57 region peptide. Live recombinant vaccines expressing beta hCG as a membrane anchored peptide generated antibody response to hCG in all animals following a single injection. CONCLUSIONS: Reversible fertility control is feasible with the HSD-hCG vaccine without impairment of ovulation or disturbance of menstrual regularity. Suggestions have been made for further optimization of the vaccine, which include replacement of TT and DT by a panel of T non B determinants communicating with the entire MHC spectrum and development of recombinant vaccine expressing beta hCG along with membrane anchored carrier.

Animals↗
PubMed1998

Preliminary studies with recombinant chorionic gonadotropin beta-subunit produced in Escherichia coli for use as an antigen in a birth control vaccine.

PROBLEM: Prototype human chorionic gonadotropin (hCG) vaccines based on natural sources are unsuitable for widespread applications due to their complex manufacturing procedures, cost, and carrier-mediated immune suppression. METHOD OF STUDY: Wistar rats were immunized with alum-adsorbed CG beta (recombinant), CG beta-TT, and nCG beta (native CG beta)-TT, whereas Bonnet monkeys were immunized with only CG beta. The anti-hCG antibody titre in the sera obtained at different time points were quantified by radioimmunoassay. The sera of Wistar rats were characterized in terms of their affinity to hCG, bioneutralization capacity (by inhibition of hCG-induced testosterone production in Leydig cells), and cross-reactivity with human luteinizing hormone, human follicle-stimulating hormone, and human thyroid-stimulating hormone (by direct binding assays). RESULTS: Antigen-binding capacities of sera obtained upon immunization with CG beta were 3,080 +/- 943 ng/ml (n = 6) and 3,993 +/- 1,292 ng/ml (n = 4), respectively, in rats and monkeys. The analysis of data revealed that immunization of rats with CG beta produced antibodies comparable to that of CG beta-TT and nCG beta-TT. CONCLUSION: The study opens up the possibility of producing pure and highly immunogenic CG beta by a recombinant DNA route, as a consistent source of antigen for birth control vaccine.

Animals↗
PubMed1998

Regain of fertility and normality of progeny born during below protective threshold antibody titers in women immunized with the HSD-hCG vaccine.

PROBLEM: Phase II clinical trials with the heterospecies dimer of beta hCG and alpha-subunit of ovine luteinizing hormone (HSD)-human chorionic gonadotrophin (hCG) vaccine showed that pregnancy was prevented at and above 50 ng/ml titers, whereas conceptions occurred below 35 ng/ml of hCG bioneutralization capacity. The effect of below-protective threshold anti-hCG antibodies on the progression of pregnancy and the normality of progeny was studied. METHOD OF STUDY: Four women enrolled by informed consent in the Phase II trials. The women studied were immunized with the HCG vaccine and did not receive booster injections in consideration of their desire to have another child. They were examined clinically at least once every month until delivery. The babies were followed up from 2 to 3.5 years, and their anthropometric indices were compared with elder siblings. RESULTS: The pregnancies progressed to 35 to 38 weeks with the usual obstetric problems, and the children developed normally. CONCLUSIONS: The anti-fertility effect of the HSD-hCG vaccine is reversible and low titers of antibodies below the protective threshold have no apparent side effects on the progression of pregnancy and on the early development of the progeny.

Adult↗
PubMed1998

Evaluation of the contraceptive potential of recombinant human ZP3 and human ZP3 peptides in a primate model: their safety and efficacy.

PROBLEM: The unique recognition events that result in the avid binding of mammalian spermatozoa to the surface of the zona pellucida (ZP) are being exploited in the development of contraceptive vaccines. In this study, the safety and efficacy of a vaccination strategy based on the induction of active immunity against purified, glycosylated, recombinant human ZP3 (rhZP3) has been evaluated in a primate model, Callithrix jacchus. METHOD OF STUDY: Long-term infertility was established after immunization with rhZP3 and the resulting immune sera reacted with rhZP3 on an enzyme-linked immunosorbent assay (ELISA) and immunolocalized exclusively to the outer surface of native ZP on marmoset ovarian sections. However, this contraceptive effect was inevitably associated with the eventual appearance of an ovarian pathology characterized by a depletion of primordial follicles. In an attempt to circumvent this side effect, human ZP3 (hZP3) was epitope mapped and four continuous, immunodominant B-cell epitopes (hZP3(45-64), hZP3(93-110), hZP3(172-190) and hZP3(341-360) were evaluated for contraceptive efficacy in vivo. Using peptide-tetanus toxoid (TT) conjugates to enhance immunogenicity, antipeptide antibodies were raised against these immunogens, which also cross-reacted with rhZP3 on ELISA. In addition, antibodies against hZP3(45-64) and hZP3(172-190) recognized native ZP on marmoset ovarian sections when a microwave technique was used to enhance epitope presentation. RESULTS: No ovarian pathology was observed after the long-term administration of these peptide immunogens, and fertility was suppressed when compared with TT controls but could not be correlated to the antibody titer. CONCLUSION: Clearly, further research is required to identify optimal B-cell epitopes that will reliably induce infertility, free from any ovarian pathology.

Amino Acid Sequence↗
PubMed1999

Oral vaccination of white-tailed deer using a recombinant Bacillus Calmette-Guérin vaccine expressing the Borrelia burgdorferi outer surface protein A: prospects for immunocontraception.

PROBLEM: Reduction of excess numbers of white-tailed deer (Odocoileus virginianus) is a prime example of a potential use for immunocontraception as a means of wildlife population management. Oral vaccination appears to be the most pragmatic way to deliver immunocontraceptive vaccines to free-roaming populations of deer, but there was little, if any, prior evidence that oral vaccination is a viable concept in deer. METHOD OF STUDY: We used live Bacillus Calmette-Guérin (BCG) in a recombinant form (rBCG), which expressed Borrelia burgdorferi outer surface protein A, to test whether deer vaccinated orally with a specific antigen expressed in a live vector produce detectable antibody titers. RESULTS: The data indicate that oral vaccination of deer with an expressed antigen is feasible, as demonstrated by peak antibody titers to the expressed antigen. Also, peak titers measured by enzyme-linked immunosorbent assay were highest in orally vaccinated deer: 1600 in deer vaccinated by injection and 6400 in those vaccinated orally. CONCLUSIONS: The results of this study demonstrate that it is feasible to vaccinate deer orally with a live vector.

Administration, Oral↗
PubMed1995

Testing the concept of virally vectored immunosterilisation for the control of wild rabbit and fox populations in Australia.

Virally vectored immunosterilisation is a concept whereby a gene encoding an antigen from an animal's reproductive system is inserted into a virus and, during infection, stimulates the formation of antibodies to that antigen such that the animal is rendered infertile. There is good evidence that certain proteins from sperm or egg when introduced parenterally will induce infertility. This paper summarises the work of the Cooperative Research Centre for the Biological Control of Vertebrate Pest Populations and reviews progress toward the isolation of the genes for gamete antigens from rabbits and foxes and their introduction into suitable viral vectors as a means of control of these pests in Australia.

Animals↗
PubMed2000

Fertilization-related sperm antigens and their immunocontraceptive potentials.

Vaccine(s) for contraception will provide an attractive alternative to contraception. There has been a renewed interest in defining fertilization-related sperm antigens that can be used for the development of a contraceptive vaccine. The sperm-zona pellucida (ZP) recognition and binding constitutes the most important event in the fertilization process, and the molecules involved at this site are attractive candidates for immunocontraception. Extensive research indicates that there are four sperm surface proteins that bind to oocyte ZP3 in humans and they belong to the four molecular regions of 95, 63, 51, and 14-18 kDa, respectively. Our laboratory is actively engaged in cloning and sequencing of cDNAs encoding for these sperm proteins and investigating the applications of recombinant (r) proteins in immunocontraception and infertility. Presently, the cDNAs encoding for the 14-18-kDa proteins, designated the NZ-1 and NZ-2, respectively, and the 51-kDa protein, designated fertilization antigen, have been cloned and sequenced. Active immunization with the rFA-1 antigen caused a reversible block/inhibition in fertility of female mice by raising a sperm/testis-specific immune response. FA-1 antigen is also involved in human immunoinfertility, and a recent clinical trial indicates that it will have a clinical application in the treatment of immunoinfertile men. The long-term goal is to employ various recombinant fertilization antigens and/or their bioeffective peptide epitopes in a single formulation, to generate an anti-sperm vaccine that will be strongly immunogenic and highly efficacious for regulation of fertility.

Animals↗
PubMed2001

Characterization of 80 kDa human sperm antigen responsible for immunoinfertility.

PROBLEM: An 80 kDa human sperm antigen (80 kDa HSA) has been identified by western blot technique using serum of an immunoinfertile woman as a probe. The 80 kDa HSA has been subsequently purified from sperm extract and investigated for antifertility effects. METHOD OF STUDY: The purified 80 kDa HSA was used to immunize adult male and female rats. Rabbit anti 80 kDa HSA antibodies were used for immunofluorescent and immunohistochemical staining to demonstrate the presence of 80 kDa HSA on the sperm and to investigate its tissue distribution. The N-terminal sequence of native 80 kDa HSA and the peptides obtained by its endoproteinase Lys-C was determined. RESULTS: Active immunization of male and female rats with 80 kDa HSA caused infertility in all the immunized animals. Immunofluorescent staining showed its localization on the head region of the human and rat spermatozoa. While immunohistochemical studies showed its localization in the testes and epididymis but not in other somatic tissues. Partial amino-acid sequence analysis showed no sequence homology with any of the known protein in the database. CONCLUSIONS: 80 kDa HSA is a promising candidate antigen for immunocontraception as it is characterized and found to cause infertility upon active immunization. specific to spermatozoa and is conserved.

Amino Acid Sequence↗
PubMed2001

Inhibition of murine sperm-oolemma binding by antibodies to an oocyte membrane (OM) antigen: implication in contraceptive vaccine development.

PROBLEM: The present study was conducted to investigate the oocyte membrane protein(s) that is involved in sperm binding in the mouse, and whether or not it can be used for the development of a contraceptive vaccine. METHOD OF STUDY: The zona-free oocytes were treated with Triton X-100 and the extract was analyzed for homogeneity in the sodium dodecylsulfate (SDS)-polyacrylamide gel electrophoresis (PAGE) after staining with silver nitrate. The appropriate band of 50+/-4 kD, designated as OM antigen, was excised from the gel and used for the immunization. The female rabbits were immunized with the excised band per se and the female mice were immunized with the OM antigen after conjugation to keyhole limpet hemocyanin (KLH). The affinity-purified antibodies were analyzed in the enzyme-linked immunosorbent assay (ELISA), immunoprecipitation procedure, western blot procedure, indirect immunofluorescence technique (IFT), and spermoolemma binding assay. Actively-immunized mice were analyzed for in vivo fertility. RESULTS: The Triton X-100 extract of zona-free oocytes predominantly showed a single protein band of 50+/-4 kD in the SDS-PAGE. Active immunization of female rabbits and of female mice with OM antigen raised high antibody titers (ELISA titer > 1:4096) that specifically recognized the OM antigen in the immunoprecipitation and Western blot procedures, and reacted with the oocyte in the IFT. These antibodies demonstrated a significant (P < 0.05) up to a complete block of sperm-oolemma binding in the in vitro binding assay. Binding of both the acrosome-intact and acrosome-reacted sperm was inhibited. Mice actively immunized with OM antigen also showed a significant reduction in vivo fertility as seen by the 9-day implants in uteri. Preliminary data indicate that the antibodies to OM antigen were tissue-specific and did not react with the specific band in any tissue extract in the western blot procedure. CONCLUSIONS: These results indicate that the OM antigen is involved in spermoolemma binding and constitute an attractive molecule that needs further investigation for examining its utility in the contraceptive vaccine development.

Animals↗
PubMed1989

Vaccination with a synthetic zona pellucida peptide produces long-term contraception in female mice.

The zona pellucida surrounding mouse oocytes is an extracellular matrix composed of three sulfated glycoproteins, ZP1, ZP2, and ZP3. It has been demonstrated that a monoclonal antibody to ZP3 injected into female mice inhibits fertilization by binding to the zona pellucida and blocking sperm penetration. A complementary DNA encoding ZP3 was randomly cleaved and 200- to 1000-base pair fragments were cloned into the expression vector lambda gt11. This epitope library was screened with the aforementioned contraceptive antibody, and the positive clones were used to map the seven-amino acid epitope recognized by the antibody. Female mice were immunized with a synthetic peptide containing this B cell epitope coupled to a carrier protein to provide helper T cell epitopes. The resultant circulating antibodies to ZP3 bound to the zona pellucida of immunized animals and produced long-lasting contraception. The lack of ovarian histopathology or cellular cytotoxicity among the immunized animals may be because of the absence of zona pellucida T cell epitopes in this vaccine.

Amino Acid Sequence↗