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Antibody response against three epitopic domains on human chorionic gonadotropin (hCG) in women and rodents immunized with a beta hCG-based immunocontraceptive vaccine.

The antibody repertoire generated against human chorionic gonadotropin (hCG), following immunization with an immunocontraceptive vaccine based on the beta subunit of the hormone, in humans was compared with that generated in rats. Three epitopic domains represented by the beta hCG loop peptide 38-57, the carboxy-terminal peptide (CTP) 109-145, and a region defined by monoclonal antibody (MAb) 206 were probed. In both species, the titer of antibodies against the MAb 206-defined epitopic domain had a good correlation with the total anti-hCG antibody titers. However, the antibody response against the beta hCG loop peptide (38-57) was not observed in human subjects and there was a weak response against this peptide in rats. Despite the good anti-hCG antibody titers in all animals (n = 8), only two had antibodies against this domain. A good antibody response was observed against CTP in rats, whereas in humans this region was weakly immunogenic. Antibodies against CTP were detected in random samples in only 57% of the subjects and this response had no correlation with the total anti-hCG antibody titers. The high antibody response against CTP in rodents compared to humans may be due to its recognition as a foreign determinant. Our results demonstrate that contraception can be achieved in women despite a poor antibody response against the CTP (109-145) and a receptor binding domain (38-57) of beta hCG.

Animals↗

[Antifertility effect of an active immunization of monkeys with human pregnancy-specific beta 1-glycoprotein (SP1) (author's transl)].

Fertile female cynomolgus monkeys (Macaca fascicularis) were actively immunized against human pregnancy-specific beta 1-glycoprotein (SP1). Native SP1 as well as chemically modified derivatives of SP1 served as antigens. The effect of the immunization on reproduction in these animals was investigated. The immunized monkeys showed a significant reduction in fertility: the conception rate in these animals was only slightly reduced when compared with the controls; but in the immunized monkeys pregnancy often resulted in abortion. The possibility of using immunization against SP1 as a contraceptive method in man is discussed.

Abortion, Spontaneous↗

Reproductive rights and population control in Zimbabwe.

The author argues that population control in Zimbabwe, in other developing countries, and even in developed countries is targeted at non-whites and at the poorer classes. She discusses fertility vaccines and male sterilization in this context, and makes the point that while the technology of population control flows from the North to the South, resources from the South are flowing North to maintain the economic status quo. "I think that the real population problem is the widening gap between a few greedy, irresponsible people, most of whom happen to be located in the North, and the rest of humankind, whose lives have been so denigrated that they are now merely statistics.... We can easily see that what should be feeding, clothing, housing, healing, pleasing Africans, goes North, all in the name of ¿development'."

Africa↗

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

Over the past 18 years, the WHO Task Force on Vaccines for Fertility Regulation has been supporting basic and clinical research on the development of birth control vaccines directed against the gametes or the preimplantation embryo. These studies have involved the use of advanced procedures in peptide chemistry, hybridoma technology and molecular genetics as well as the evaluation of a number of novel approaches in general vaccinology. As a result of this international, collaborative effort, a prototype anti-HCG vaccine is now undergoing clinical testing, raising the prospect that a totally new family planning method may be available before the end of the current decade.

Animals↗

Evaluation of zona pellucida antigens as potential candidates for immunocontraception.

Antibodies directed against the zona pellucida can interrupt sperm-egg recognition in vitro. However, the mechanisms by which anti-zona antibodies exert this contraceptive effect in vivo remain uncertain. There is an accumulating body of evidence to suggest that active immunity against zona antigens not only induces infertility via an antibody-mediated interruption of sperm--egg interaction but also disrupts normal ovarian function. We have evaluated the consequence of inducing active immunity against purified recombinant human ZP3 (rec.hZP3) and human ZP3 peptides, using the marmoset monkey, Callithrix jacchus, as an animal model. Although infertility was established in animals that received rec.hZP3, it was associated with ovarian dysfunction characterized by suppression of folliculogenesis and depletion of the primordial follicle pool. Immunization with continuous human ZP3 peptides, identified by epitope mapping studies, did not induce ovarian pathology but the antibody titres were insufficient to suppress fertility significantly and consistently. Clearly, further research is required to identify and segregate epitopes on the zona glycoproteins that are capable of inducing infertility without any side effects.

Animals↗

Tissue specificity of the acrosomal protein SP-10: a contraceptive vaccine candidate molecule.

The tissue specificity of the intra-acrosomal protein SP-10 was examined by Northern blot and polymerase chain reaction (PCR) analysis. Messenger RNA from 36 tissues in the female baboon (Papio papio) was isolated, separated on agarose gels, transferred to nylon, and probed with either SP-10, beta-actin, or cyclophilin cDNA. Northern blots, which were processed at both low and high stringency, showed SP-10 to be expressed exclusively in the testis. The mRNA from each tissue was also reverse transcribed, and both SP-10 and beta-actin were amplified by PCR from the resulting cDNA. Ethidium bromide-stained agarose gels of the SP-10 PCR products showed three clear bands from the testis but no co-migrating bands from the other tissues. Southern blots of the PCR products showed that only the three bands in the testis were related to SP-10. The data demonstrate that the SP-10 gene products are testis specific, a characteristic essential for a contraceptive vaccine candidate molecule.

Acrosome↗

A practicable immunological approach to block spermatogenesis without loss of androgens.

The intrinsic capacity of the immune system to elicit immune response selectively against late developing sperm proteins has been mobilized to intercept spermatogenesis. Bacillus Calmette-Guérin given in appropriate doses intratesticularly is effective in bringing about this effect. In dogs and rhesus monkeys, the sperm count in the semen declined precipitously, and almost complete azospermia was attained in 4-6 weeks after immunization. The few sperm cells that were present were immotile. Examination of serial sections of testes in immunized rats showed about 98% of the tubules to be devoid of sperm. The tubules were partially or fully atrophied. The basement membrane was, however, intact and the pertubular cell layer was normal. Sertoli cell nuclei were apparently normal but the cytoplasm was vacuolated and, in most cells, partially disintegrated. The lumen of the tubules was exhausted of formed elements and at times filled with eosinophilic debris. Leydig cells were present and hyperplasia of interstitial cells was seen, with massive infiltration of leukocytes. Blood testosterone levels were in the normal range and Leydig cells were responsive to gonadotropins. Libido was intact. The method was applicable to a variety of mammalian species. The implications of the results are discussed.

Adjuvants, Immunologic↗