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  1. 1

    [Immunocontraception -- current research status] Immunkontrazeption -- jetziger Stand der Forschung.

    von Ditfurth M; Pelzer V

    GYNAKOLOGE. 1990 Jun; 23(3):178-83.

    In 1972, WHO advanced the idea of a safe and reversible birth control vaccine lasting 1-2 years. This contraceptive could utilize the connection of sperm antibodies and sterility by active immunization (foreign antigens) and passive immunization (monoclonal antibodies). After long experimentation, a vaccine was introduced in 1984 based on the carboxyl-terminal peptide (CTP) of the beta subunit of human chorionic gonadotropic (HCG) couples with a diphtheria toxoid (DT) and mixed with a muranyldipeptide (MDP) adjuvant called 109-145-CPT-beta- HCG:DT mixed with MDP. When given to baboons, the pregnancy rate fell to 4.6% vs. the 70% rate in untreated animals. Out of 15 women with previous tubal ligations, 14 showed production of specific antibodies: in Group A, 80 ug beta-HCG antigen was injected 4 times 2 weeks apart, while Group B received 240 ug only twice, 1 month apart. Side effects included edema, adnexal pain, DNA-antibody increase, plasmacortisone fluctuations, and liver enzyme changes. Later refinements eliminated blood chemistry changes, and injection 4 times produced specific antibody formation after 500 days. Immunization against follicle stimulating hormone (FSH) produced reversible sterility in rhesus monkeys after 4 and 1/2 years; however, the controversial role of testosterone in spermatogenesis terminated this approach. The inactivation of LDH-C4-lactatedehydrogenase produced only reduction of fertility in rabbits and baboons. However, 25 guinea pigs immunized twice, 1 month apart, with PH 20, a sperm-coating antigen, exhibited 100% infertility compared to the fact that 94% of untreated controls had a litter. Zona-pellucida antigens affected not only the egg cells but also the ovarian follicles. Among embryonal antigens, F-9-oncofetal antigens reduced fertility in mice but produced teratocarcinoma. Passive immunization by mono- and polyclonal antibodies against early- pregnancy factor terminated pregnancy in mice, suggesting another possible avenue for immunocontraception.
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  2. 2

    Diphtheria, pertussis, and tetanus vaccination [letter]

    Cutts FT; Begg N

    Lancet. 1992 May 30; 339(8805):1355-6.

    Researchers compared the immune responses of infants vaccinated at 2, 3, and 4 months of age with the diphtheria-pertussis-tetanus (DPT) conjugate vaccine with those of infants vaccinated at 3, 5, and 9 month intervals. The antibody titer for pertussis was the same for both the old and new schedules. Further, no reliable immunological correlates of protection existed for pertussis. Different batches of DPT vaccine and maternal antibodies may have accounted for the variation in immune responses. No one measured maternal antibodies in the infants in the 3, 5, and 9 month group, though. The protective level of antitoxin for tetanus and diphtheria (0.01 neutralizing units/ml) cannot be applied to ELISA assays, since the relationship between the 2 assays is inadequate at levels less than 0.1 IU/ml. 1964 research of 9 injection schedules showed that when infants received the first dose at 3 months rather than later, or when the intervals were 1 month long instead of 2 months, diphtheria and tetanus antitoxin titers were lower 2 weeks after series completion. Therefore, clinical researchers should do lengthy longitudinal studies of infants vaccinated at 2, 3, and 4 months before the clinicians can actually determine the persistence of immunity to school entry. The UK Public Health Laboratory Service is doing a longitudinal study of early and long term antibody responses to the new schedules. In fact, the accelerated vaccination schedule has improved coverage during the first year of life. 20-30% of pertussis cases are less than 6 months old in developing countries. WHO's Expanded Programme on Immunization encourages health workers to begin vaccine series as early in life as possible and to keep the intervals as short as possible. Even though no primary series of 3 doses of DPT protects an infant for a lifetime, health workers should achieve high coverage with early doses and shorter intervals. WHO already advocates giving women of reproductive age in developing countries 5 doses of tetanus toxoid to reduce neonatal deaths.
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  3. 3

    The WHO Task Force on Vaccines for Fertility Regulation. Its formation, objectives and research activities.

    Griffin PD

    HUMAN REPRODUCTION. 1991 Jan; 6(1):166-72.

    The WHO Task Force on Vaccines for Fertility Regulation is one of several Task Forces, consisting of international, multidisciplinary groups of scientists and clinicians collaborating in research on specific goals, established in 1972. Its accomplishments are reviewed here. The Task Force convened a meeting in 1974 to select criteria for tissues and molecules capable of mounting antifertility responses. These molecules had to be restricted to the target tissue, sequestered in the reproductive tract, present transiently, and chemically characterized. Some of the antigens considered were sperm enzymes and membranes, as well as a data bank of sera naturally immunized against sperm. Other were anti-ovum and placenta molecules such as zona pellucida, the SP-1 placental antigen, and the placental hormones chorionic somatotrophin and human chorionic gonadotropin (hCH). Trophoblast-derived monoclonal antibodies and gene libraries are being screened. Anti-hCH is the vaccine composed of a portion of the beta subunit complexed to a carrier antigen, diphtheria toxoid, in a water- oil emulsion with an adjuvant has been tested in a phase I clinical trial in 1986-1988. A Phase II trial is being planned to see if the immune response in women is large enough to be capable of preventing pregnancy. Further improvements in the vaccine are being envisioned, such as incorporation of the peptide carrier conjugate and immune stimulant into biodegradable microspheres, hopefully to produce a longer-lasting immunity and a more stable vaccine. While the WHO Task Force on Vaccines for Fertility Regulation has been forced to cut back on some avenues of research, its success has stimulated other centers to take up several important projects, e.g. the sperm LDH and zona pellucida vaccines.
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  4. 4

    Immunobiology of human chorionic gonadotropin.

    Gupta SK; Singh V


    A comprehensive review of the immunobiology of human chorionic gonadotropin (hCG), including the structure of both alpha and beta chains, immunogenicity of various segments and epitopes of each, secretion and function of the hormone, determinants of receptor recognition, and finally, clinical studies of possible contraceptive beta-hCG-based vaccines, is presented. hCG is composed of 2 glycosylated peptides. The alpha subunit is identical to that found in hLH, hFSH and hTSH. The beta subunit, which is limiting in the sense that it is secreted in smaller amounts, defines the biological activity of hCG. hCG is secreted throughout pregnancy from 170 hours after fertilization to a peak at 8-10 weeks of and is essential for maintenance of early pregnancy by progesterone secreted by the corpus luteum. Although native hCG evokes antibodies, they cross react with LH, so such a vaccine would not be useful for contraception. Beta-hCG has been purified and also produced by monoclonal antibodies, and shown to produce antibodies and infertility in baboons. Phase I clinical trials of immunologically purified beta-hCG complexed to tetanus toxoid were conducted on 63 women in an international study in the mid-1970s, but results were mixed in terms of antibody titer and duration. New vaccines have been designed based on more sophisticated adjuvants, beta- hCG-terminal peptides, and polyvalent vaccines and are being tested in 4 Phase I trials currently, sponsored by the Population Council, the Indian government-sponsored program, and the WHO.
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  5. 5
    Peer Reviewed

    Developments in pertussis vaccines: memorandum from a WHO meeting.

    Griffiths E; Kreeftenberg JG


    The WHO memorandum outlines the present situation regarding pertussis vaccines, discusses ways to evaluate candidate vaccines, and identifies future research needs. Most existing whooping cough vaccines are whole-cell vaccines, combined with diphtheria and tetanus toxoid adsorbed on an aluminum or calcium carrier. As whole bacterial cells, they contain a complex array of at least 7 toxins and antigens, and display a narrow margin between potency and toxicity. The Japanese introduced an acellular vaccine, admittedly sometimes less potent, called the Precipitated Purified Pertussis Vaccine, in 1981. This material contains far less bacterial mass, notably less endotoxin, and consequently produces less fever, erythema and induration. WHO has not yet established minimum requirements for standardization; even the mouse potency assay may not be suitable. There are techniques, however, which will measure amounts of component antigens and toxicity. Conflicting results on assays of potency and immunogenicity will have to be resolved. Besides the obvious need for large clinical trials of defined vaccines, a whole range of research needs were suggested, from genetic studies of the organism to specific details of the host response. It is generally agreed that a less reactogenic and more effective pertussis vaccine is needed and feasible.
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