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PubMed1996

Primate response to immunization with a homologous zona pellucida peptide.

Development of a contraceptive vaccine using zona pellucida (ZP) antigens has been hampered by the observation that the immune response to the antigens results in altered ovarian function and depletion of the follicular pool of oocytes. The amino acid sequences of many ZP proteins have been determined in the past decade allowing study of fully synthetic peptide immunogens based on these ZP sequences. Such immunogens permit a precisely targeted response. The non-human primate is the best model for predicting how women may respond to ZP peptide vaccines. Cynomolgus macaques (Macaca fascicularis) have been immunized with synthetic peptides comprising a human ZP3 epitope and a macaque homologue of the same epitope. In both studies, immune response to the peptides was initiated, and infertility was accompanied by normal ovarian function.

Animals↗
PubMed1996

Applications of pig zona pellucida immunocontraception to wildlife fertility control.

A unique application of pig zona pellucida (PZP) immunocontraception is the control of wildlife populations. A native PZP vaccine has been successfully applied to wild horse and donkey populations. A single annual booster inoculation was capable of maintaining contraception. Seven consecutive years of PZP treatment in wild mares resulted in no detectable debilitating side effects, and reversibility of contraception has been documented among mares treated for up to 4 consecutive years. Long-term treatment (5-7 years) is associated with some ovulation failure and depressed urinary oestrogen concentrations. Complex social behaviours in horses were unaffected by treatment. PZP immunocontraception has also been successfully applied to white-tailed deer, with no detectable changes in ovarian histology after 2 years of treatment. Seventy-four species of captive zoo animals have been treated with the PZP vaccine, with documented success in 27 species, including members of the orders Perissodactyla (Equidae), Artiodactyla (Cervidae, Capridae, Giraffidae, Bovidae), and Carnivora (Ursidae, Mustelidae, Felidae). Immunocytochemistry studies have demonstrated a high degree of crossreactivity between anti-PZP antibodies and African elephant zona pellucida. The need for a one-inoculation form of the vaccine has led to the incorporation of PZP into lactide-glycolide microspheres, which cause a delayed release of the PZP. PZP immunocontraception of wildlife has potential because of (1) > 90% effectiveness, (2) the ability for remote delivery, via darts, (3) reversibility after short-term use, (4) a wide breadth of effectiveness across many species, (5) a lack of debilitating side-effects even after long-term treatment, and (6) minimal effects upon social behaviours.

Animals↗
PubMedDate not supplied

Human chorionic gonadotropin as a target for cancer vaccines.

Human chorionic gonadotropin (hCG) is expressed by common cancers and may play a role in cell transformation as well as angiogenic, metastatic, and immune escape phenomena that are central to cancer progression. Clinical trials with a vaccine targeting the carboxy-terminal peptide of -hCG have indicated that tolerance to this oncofetal antigen can be broken. Humoral responses that may modulate the biologic activity of tumor-associated hCG as well as cellular responses to hCG have been generated. Studies are in progress to further define the biologic significance of hCG in cancer and to develop a vaccine approach that will best target this expression.

Alleles↗
PubMed2003

Status of immunodiagnosis and immunocontraceptive vaccines in India.

The article focuses on the Indian initiative of making kits for diagnosis of various infectious and non-infectious diseases as well as reproductive hormones and hormones in various other endocrine disorders. Indigenous diagnostic kits for the detection of various infections such as filariasis, typhoid, amebiasis, Japanese encephalitis, hepatitis, HIV, dengue, leishmaniasis, malaria, rabies, toxoplasmosis, rotavirus, and group A streptococci have been developed. Agreements to transfer the know-how of some of these leads to industries have been signed. The know-how of enzyme-linked immunosorbent assay (ELISA) for detection of hepatitis C has been successfully transferred to industry and is being commercially produced. For detection of HIV-1 and HIV-2, indigenous diagnostic kits based on three different formats, namely ELISA, Western blot and rapid test have been developed and are being commercially produced by Indian industries. The factors influencing the successful transfer of laboratory-scale diagnostic assays from academia to industry and their commercial exploitation have been discussed. Indian scientists have made seminal contributions in exploring the possibility to develop an effective and safe contraceptive vaccine to control the increasing human population of India. Achieving contraception by means of vaccine is a novel approach, which entails generation of a specific antibody response against antigens critically involved in the process of mammalian reproduction. In India, three major programs on contraceptive vaccines based on the beta-subunit of human chorionic gonadotrophin ((beta)hCG) for women, ovine follicle stimulating hormone (oFSH) for men, and riboflavin carrier protein for both males and females have been initiated. The work at the National Institute of Immunology, New Delhi on contraceptive vaccine for women, based on (beta)hCG, has demonstrated, for the first time, that it is feasible to regulate fertility by such an approach. Basic research being carried out to achieve immunocontraception by interfering at sperm-oocyte interaction level has been briefly discussed. These developments are still at the research stage. In addition to advances in the area of contraceptive vaccines, a non-steroidal contraceptive oral pill has been developed by Central Drug Research Institute, Lucknow, commercially produced by two Indian pharmaceutical companies and has been incorporated in the National Family Welfare Program. Another interesting approach for fertility regulation in male has been developed in India, which involves vas occlusion with styrene maleic anhydride (SMA) and is currently undergoing clinical trials in human subjects.

Biotechnology↗
PubMed1997

Sperm antigens and their use in the development of an immunocontraceptive.

PROBLEM: Overpopulation is a global problem of significant magnitude, with grave implications for the future. World population is predicted to reach 10 billion people by the year 2050, an increase of more than 75% over the current population. Development of new contraceptives is necessary, since current forms of birth control are unavailable to many individuals due to sociological, financial, or educational limitations. METHODS: In an effort to identify new contraceptive alternatives, sperm-specific antigens are under the investigation as the basis for immunological regulation of fertility through contraceptive immunization. Anti-sperm antibodies (ASA) inhibit sperm function in vitro, induce infertility in experimental models, and have been implicated in some cases of clinical infertility. Furthermore, the development of ASA in vasectomized men does not lead to physiological complications despite the persistence of these antibodies for years; thus, ASA induced by immunization of men and women may be similarly harmless. Immunization has several conceptual advantages as a method of fertility regulation. Employment of non-pharmacologically active agents, convenience of administration, low cost, and the potential for relatively long-lasting yet reversible effects. RESULTS: Various approaches have been taken to identify candidate sperm antigens for immunocontraceptive development. Studies that utilized monoclonal antibodies and polyclonal antisera generated against sperm preparations have identified such promising candidates as PH-20, fertilin, SP-17, and SP-10. In animal model, 100% contraceptive effects were induced following PH-20 immunization and the effects were reversible. More recently, ASA from the sera of infertile patients were employed to identify several candidates as expressed by testis cDNA libraries. Perhaps the most extensively characterized and effective immunogen candidate identified thus far is lactate dehydrogenase-C4 (LDH-C4). Active immunization with LDH-C4 suppressed fertility in a variety of mammalian species, including primates, and the reversibility of these effects was demonstrated. CONCLUSION: The successful results obtained thus far support the feasibility of an effective immunocontraceptive and indicate the importance for continued investigation of additional sperm antigens as contraceptive immunogen candidates.

Contraception, Immunologic↗
PubMed1994

Development of an antifertility vaccine for pets based on active immunization against luteinizing hormone-releasing hormone.

Male dogs and cats were immunized against LHRH in order to evaluate the feasibility of an immunological approach to pet contraception. In the first study, dogs were immunized with 100, 500, or 2500 micrograms of LHRH conjugated to tetanus toxoid. A significant decline in serum testosterone (T) levels was observed in all immunized dogs, reaching castration levels in some animals by Week 4 and remaining suppressed in all the immunized dogs through the course of the study. Testicular histology suggested arrest of spermatogenesis (infertility). The effects of "immunological castration" were reversible (study 2): steroidogenesis suppressed by "immunological castration" was restored as antibody titers declined. Effective antibodies were rapidly reinduced in dogs by a single injection of LHRH1-TT. In contrast, the level of antibodies induced in male cats (study 3) was not sufficient for "immunological castration." The conclusion was that active immunization against LHRH could provide a cost-effective, nonsurgical, reversible means to control the fertility of companion animals.

Animals↗
PubMed1979

[Chromogenic and immunological determination of antithrombin III and of antiplasmin in subjects under treatment with oral hormonal contraceptives].

We have effectuated a chromogenic and immunologic determination of alpha 2-At III and antiplasmin in plasma into three groups of patients. The 1st group is constituted of 93 subjects which never take oral hormone contraceptives. The 2nd group is constituted of 56 subjects who are taking oral hormone contraceptives. The 3rd group is constituted of 55 subjects in pregnancy (VI-VIII months). The results show a light difference, in the immunologic assay, between I in equilibrium or formed of II and I in equilibrium or formed of III, but there is not a significant difference in the chromogenic determination. Data have not evidenced significant variations in the antiplasmin too, except for the group of subjects in pregnancy.

Adult↗
PubMed2004

Update on zona pellucida glycoproteins based contraceptive vaccine.

Zona pellucida (ZP) glycoproteins, due to their critical role in mammalian fertilization, have been proposed as candidate immunogens for development of a contraceptive vaccine. Active immunization studies in a variety of animal species, employing either native or recombinant zona proteins, has established their contraceptive potential. Hence, ZP glycoprotein-based contraceptive vaccines have a very good potential for controlling wild life population. To make it a realistic proposition, additional research inputs are required to develop new potent adjuvants and novel practical strategies for vaccine delivery. The observed ovarian dysfunction, often associated with immunization by ZP glycoproteins, is one of the major obstacles for their application in the control of human population. Ongoing studies to delineate epitopes of ZP glycoproteins that will generate an immune response capable of inhibiting fertility without any untoward effects on ovarian functions will help in determining their feasibility for human use.

Adjuvants, Immunologic↗
PubMed1997

Plant immunomodulators for termination of unwanted pregnancy and for contraception and reproductive health.

Neem (Azadirachta indica) seed and leaf extracts have spermicidal, anti-microbial, anti-fungal and anti-viral properties. They are also immunomodulators that induce primarily a TH1 type response. These properties are being exploited to develop two different useful methods of fertility control. Neem extracts given orally at early post-implantation stage terminate pregnancy in rodents and primates. Treatment has no residual permanent effect and fertility is regained in subsequent cycles. The mechanism by which the action occurs is not fully clear. A transient increase in CD4 and more significantly in CD8 cells is noticed in mesenteric lymph nodes and spleen. A rise in immunoreactive and bioactive TNF-alpha and IFN-gamma in draining lymph nodes, serum and foetal-placental tissue is observed. A polyherbal cream and pessary have been developed containing three active ingredients of plant origin. These have synergistic spermicidal properties on human sperm as determined by the Sander Cramer test. Their use before mating has high contraceptive efficacy in rabbits and baboons. Another interesting property is their inhibitory action on a wide spectrum of micro-organisms, including Candida albicans, C. tropicalis, Neisseria gonorrhoeae, the multidrug-resistant Staphylococcus aureus and urinary tract Escherichia coli, Herpes simplex-2 and HIV-1. Phase I clinical trials have been completed in India, Egypt and the Dominican Republic, and indicate the safety of the formulation, its acceptability and beneficial action invaginosis due to infections.

Abortion, Induced↗
PubMed1976

A review of recent developments in human fertility control.

Recent and significant developments in the field of fertility control are reviewed. Consideration is given to new aspects of existing methods, recent modifications to steroidal formulations and Intrauterine devices, increased utilization of older methods (abortion and sterilization) and evaluation of new fields (postcoital contraception, prostaglandins and immunological techniques). There is an increasing demand for better application of newly developed methods and a rational decision in the selection of appropriate methods.

Abortion, Induced↗
PubMed1981

Vascular thrombosis and oral contraceptives - a risk correlated study.

An immunological mechanism of the vascular complications related to oral contraceptives (O.C.) was suggested by the demonstration of circulating anti-ethinylestradiol antibodies in several cases. According to the characteristics of the specific immunoglobulins (Ig), a test based upon Ig precipitability in 25% saturated ammonium sulfate was developed. This test was applied to several groups of women on O.C. with and without thrombosis, and to a control group. Results indicated: (1) that the test was positive in nearly 100% of women with a vascular thrombosis on O.C.; and (2) that the test could detect among healthy contraceptive users a group of women who may be considered as at risk. The role of adjuvant factors is considered.

Adult↗
PubMed1984

Mouse lactate dehydrogenase (LDH) C4 (testis) is immunochemically cross-reactive with LDH A4 (muscle) and LDHB4 (heart).

It has been reported that lactate dehydrogenase (LDH) purified from testes (LDH C) of homotherms is not immunochemically cross-reactive with somatic forms of LDH purified from heart (LDH B) or muscle (LDH A). On the basis of this premise, LDH C has been considered for use as a contraceptive vaccine. Data presented here indicate that mouse antisera to either mouse or rat LDH C are cross-reactive with LDH A and B purified from muscle and heart tissues of mice. However, rabbit antisera to mouse LDH C are not cross-reactive with either mouse LDH A or B. Thus, the degree of cross-reactivity is dependent on the species from which the immunogen LDH is purified, the antisera are derived, and the LDH used in the assay is purified. The determination that LDH A, B, and C are immunochemically cross-reactive is of importance in evaluating LDH C as an immunogen in an immunologic approach to contraception.

Animals↗
PubMed1990

Relevance of immuno-contraceptive vaccines for population control. I. Hormonal immunocontraception.

Human chorionic gonadotropin--subunit beta (beta-hCG) has been so far most extensively studied antigen for immuno-contraceptive properties. Studies of vaccination of non-human primates has been so far controversially reported since some antisera obtained from baboons immunized with beta-hCG had shown cross-reactivity to other tissues. Despite these problems and concerns about the complete safety of this first generation vaccine, a decision has been made to proceed with a limited clinical trials with this vaccine. Results from these trials are encouraging and indicate that contraceptive antibody titers can be achieved with permissible adjuvants. Neutralization of LH and/or FSH by circulating antibodies may impede their action and interfere with the maturation of gametes. Gonadotropin releasing hormone can be also a suitable target for immunological attack.

Chorionic Gonadotropin↗
PubMed2002

Effects of GnRH agonist (leuprolide) on reproduction and behaviour in female wapiti (Cervus elaphus nelsoni).

Fertility control offers a potential alternative to traditional methods for regulating the growth of overabundant wild ungulate populations. However, current technology is limited due to practical treatment application, undesirable side-effects and economic considerations. A promising non-steroidal, non-immunological approach to contraception involves the use of a potent GnRH agonist. Two experiments were conducted to evaluate the effectiveness of a GnRH agonist (leuprolide) for controlling fertility in captive female wapiti and to assess physiological and behavioural side-effects of the treatment. In Expt 1, the optimum dose of agonist treatment was determined by measuring serum LH response of eight female wapiti to four formulations of leuprolide (0, 45, 90 and 180 mg) administered as a subcutaneous (s.c.) bioimplant. In Expt 2, the effects of leuprolide on wapiti pregnancy rates, duration of suppression of serum LH and progesterone secretion, and short-term behavioural and physiological side-effects were evaluated. All concentrations of leuprolide in Expt 1 were equally effective in reducing serum LH to non-detectable values throughout the 130 day trial. In Expt 2, leuprolide administered before the breeding season was 100% effective at preventing pregnancy in treated females. Serum LH and progesterone were reduced to baseline values by day 92 and remained at this concentration for 195-251 days after treatment, and returned to pretreatment concentrations in the following breeding season. Reproductive behaviour rates were similar for treated and untreated wapiti for all behaviour categories for both the breeding and post-breeding seasons. Haematology and blood chemistry parameters of treated and un-treated females were similar, and seasonal intake and body weight dynamics appeared normal. In conclusion, leuprolide is a safe, effective contraceptive agent and can potentially suppress fertility in female wapiti for one breeding season.

Animals↗