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BRITISH MEDICAL BULLETIN. 1993 Jan; 49(1):88-99.The 3 primary candidates for the development of a contraceptive vaccine are: a) human chorionic gonadotropin (hCG), b) the zona pellucida, and c) the sperm surface. The most advanced approach involves the induction of immunity against hCG. Completed Phase I clinical trials have revealed that such preparations are capable of stimulating the production of anti-hCG antibodies. Phase 2 studies are about to commence. Vaccines are being engineered based on conjugates which incorporate tetanus or diphtheria toxoid linked to a variety of hCG-based peptides centered on the beta-subunit of this molecule. However, the longterm safety of efficacy of such immunity is unknown. The remaining 2 vaccine development approaches aim to prevent conception by interfering with the interactive events that characterize the union of male and female gametes of fertilization. The zona glycoprotein, ZP3, is a prime candidate for such a vaccine, in the view of its important role in the recognition and activation of spermatozoa and its unique antigenic composition. A major problem with this approach involves the loss of primordial follicles observed in the many in vivo studies in which active immunity against this protein has been induced. The possibility that this problem can be overcome by identifying B-cell epitopes that will avoid the T-cell responses thought to be responsible for the appearance of ovarian dysfunction is now being actively investigated. Disruption of fertilization through the induction of immunity against sperm surface antigens is a third approach, for which there is clinical support as patients have exhibited infertility associated with the appearance of spontaneous immunity against sperm antigens. Potential targets are constrained by considerations of immunogenicity, specificity, antigen density, and location.
The WHO Special Programme of Research, Development and Research Training in Human Reproduction and its Task Force on Vaccines for Fertility Regulation.
In: Reproductive immunology 1986, [edited by] D.A. Clark and B.A. Croy. Amsterdam, Netherlands, Elsevier Science Publishers, 1986. 154-61.In the early 1970s the WHO's Special Program of Research, Development and Research Training in Human Reproduction was formed. Its objectives were to study new methods of fertility regulation and infertility, to disseminate information, and to aid research in developing countries. 9 task forces conduct research in sundry areas. Highly effective, long- acting, injectable contraceptives are used by 3.5 million women worldwide, but these agents produce menstrual bleeding disorders and amenorrhea. Other research subjects are biodegradable contraceptive, implants, which deliver constraint amounts of a drug during a 2-year period; a levonorgestrel-releasing vaginal ring, delivering a tiny amount of progestogen; new post-coital drugs effective during a first 5 weeks post-ovulation; sperm antigens, ovum antigens, and hormonal and non-hormonal antigens of the trophoblast and early placenta. Hyaluronidase and acrosomal protease, which are involved in the spermatozoa's penetration of the cumulus cells and zona pellucida of the ovum, respectively, can elicit high antibody responses. Encouraging findings were obtained with the sperm-specific isozyme, lactic dehydrogenase C-4. Ovum antigens directed at zona pellucida (ZP) demonstrated that antibodies can prevent sperm attachment. Immunization of female baboons with whole porcine ZP produced an antifertility effect. Two hormonal placental antigens, human placental lactogen, and human chorionic gonadotrophin (hCG) were also studied to develop an anti-hCG vaccine consisting of a synthetic peptide conjugated to diphtheria toxoid and mixed with a muranyl dipeptide adjuvant. Another line of inquiry was to determine if an anti-sperm immune response restricted to the lumen of the female genital tract could be elicited by application of acrosin and hyaluronidase to the cervix. The antibody profiles of the are of individuals with unexplained infertility were compared with those of fertile controls to identify certain immune responses that were consistently linked to infertility.
Central African Journal of Medicine. 1985 Feb; 31(2):22-4.A great deal of activity is being focused on the possibility of developing an effective vaccine for malaria. Drug resistance is the main problem. Of the new drugs under examination, only meflaquine, a quinine analogue, is at the stage of a clinical trial and even here it appears that resistance may be a problem. This review summarizes the current state of research on malaria immunization and adds some Zimbabwean perspectives. Natural immunity to malaria is directed against the blood stages of the parasites and is mediated by both humoral and cellular mechanisms. Resistance to malaria in both humans and animals can be transferred by passive immunization using immunoglobin infusions. Evidence indicates that the spleen has a central role in resistance to malaria. Malarial infection is known to be associated with immunosuppression. Of considerable practical importance is the observation that antibody responses to irradiated sporozoites in rodents were suppressed by acute Plasmodium berghei infection. Immunity is species specific, develops slowly and is short lived. There are 3 stages in the malaria life cycle at which immunization might be expected to be effective: the sporozoite, merozoite and gametocyte stages. 95% of malaria in Zimbabwe is caused by Plasmodium falciparum. A major requirement for effective immunization is an antigen preparation, which, while causing no harmful effects in itself will stimulate an immune response capable of inactivating the infective agent in question. A significant breakthrough has been achieved by Ruth Nussensweig and her colleagues using the techniques of molecular biology. There is a wide variation in the body's response to injected malarial antigens. Repeated injection with irradiated sporozoites (which are incapable of multiplying in the body) are able to induce shortlived immunity in man. Funding problems also exist in developing a useful vaccine; much of the research is funded by the WHO.