Effects of Immunization with the β-Subunit of Ovine Luteinizing Hormone on Corpus Luteum Function in the Rhesus Monkey

Thau, Rosemarie B.; Sundaram, K.; Thornton, Yvonne S.; Seidman, Linda S.

doi:10.1016/s0015-0282(16)43823-9

Cited by 46 publications

(2 citation statements)

References 8 publications

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“…Nonneutralized LH appears to be sufficient to induce ovulation even after partial neutralization by antibodies. This has also been observed in rhesus monkeys immunized with the (3 subunit ofovine LH (22). The LH cross-reaction does not cause sufficiently deficient corpus luteum function since menstrual cycle regularity is maintained.…”

Section: Discussionmentioning

confidence: 63%

A vaccine that prevents pregnancy in women.

Talwar

Singh

Pal

et al. 1994

Proc. Natl. Acad. Sci. U.S.A.

200

134

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We report here results of clinical trials on a birth control vaccine, consisting of a heterospecies dimer of the .3 subunit of human chorionic gonadotropin (hCG) associated noncovalently with the a subunit of ovine luteinizing hormone and coijugated to tetanus and diphtheria toxoids as carriers, that induces antibodies of high avidity (Ka 1010 M-) against hCG. Fertile women exposed to conception over 1224 cycles recorded only one pregnancy at antibody titers of >50 ng/ml (hCG bioneutralization capacity). The antibody response declines with time; fertility was regained when titers fell to <35 ng/ml. This study presents evidence of the feasibility of a vaccine for control of human fertility.A number of contraceptive methods are available; they do not, however, suit all potential users. There is need to develop additional methods, in particular those that are reversible, require only periodic intake, and do not disturb menstrual regularity or bleeding. Vaccines regulating fertility offer promising prospects to meet these specifications. The rationale for these vaccines is to induce the formation of antibodies and/or cell-mediated immunity to intercept selectively a process critical to the success of reproduction. A number of potential antigens are being investigated (1-7). Among these are hormones, which play an important role in the regulation of fertility. Human chorionic gonadotropin (hCG) is an early signal of conception and is considered essential for establishment and maintenance of early pregnancy. An advantage in choosing hCG as a target for immunocontraception is that its inactivation would not interfere with other physiological processes in the female, such as ovulation and production of sex steroid hormones.Carrier conjugation with tetanus toxoid (TT) was proposed as a strategy to overcome the immunological tolerance of a woman against hCG (8). This initial prototype vaccine (/3hCG-TT adsorbed on alum) had limitations. It induced high antibody titers in only a small percentage of women, and those with low titers were not protected from pregnancy (9). Three changes were made to enhance immunogenicity.(i) An adjuvant, the sodium phthalyl derivative of lipopolysaccharide, was included in the first injection. This nonpyrogenic adjuvant is usable in aqueous phase (10). Its use doubled, on average, anti-hCG titers and increased the frequency of high responders.(ii) The intrinsic immunogenicity of (3hCG was enhanced by associating it noncovalently with the a subunit of ovine luteinizing hormone (LH) to form a heterospecies dimer (HSD), a laboratory-made hormone that attains a conformation which recognizes receptors on target tissues (whereas isolated subunits do not) and generates a steroidogenic response even superior to that by hCG (11). HSD linked to carriers was indeed found to be more immunogenic than ,8hCG in rats and monkeys (12). Moreover, the antibodies had better capacity to neutralize the bioactivity of hCG (11,13 It was important to determine whether the antibodies induced by the HSD-and 8hC...

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Section: Discussionmentioning

confidence: 63%

A vaccine that prevents pregnancy in women.

Talwar

Singh

Pal

et al. 1994

Proc. Natl. Acad. Sci. U.S.A.

200

134

View full text Add to dashboard Cite

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“…Since FSH, LH, and thyroid-stimulating hormone (TSH) share the same α subunit [14], antibodies produced by vaccination against FSH or LH react with TSH [15,16]. In order to avoid cross-immunity, the recombinant β subunits of LH (β-LH) [17,18] and FSH (β-FSH) [19,20] were developed as immunogens. Though the β-FSH vaccine has higher targeting specificity, the binding affinity of β-FSH antibody to FSH is lower by one order of magnitude compared to antibodies generated against the intact FSH [21].…”

Section: Introductionmentioning

confidence: 99%

Effects of Vaccination against Recombinant FSH or LH Receptor Subunits on Gonadal Development and Functioning Male Rats

Pan,

Fu,

Zhang

et al. 2024

Veterinary Sciences

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Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) play key roles in regulating testosterone secretion and spermatogenesis in male mammals, respectively, and they maintain the fertility of male animals by binding to their corresponding receptors. We designed and prepared a recombinant LH receptor (LHR) subunit vaccine and a recombinant FSH receptor (FSHR) subunit vaccine and used male Sprague Dawley (SD) rats as a model to examine their effects on testicular development, spermatogenesis, and testosterone secretion in prepubertal and pubertal mammals. Both vaccines (LHR-DTT and FSHR-DTT) significantly decreased the serum testosterone level in prepubertal rats (p < 0.05) but had no effect on the testosterone secretion in pubertal rats; both vaccines decreased the number of cell layers in the seminiferous tubules and reduced spermatogenesis in prepubertal and pubertal rats. Subunit vaccine FSHR-DTT decreased the sperm density in the epididymis in both prepubertal and pubertal rats (p < 0.01) and lowered testicular index and sperm motility in pubertal rats (p < 0.05), whereas LHR-DTT only reduced the sperm density in the epididymis in pubertal rats (p < 0.05). These results indicate that the FSHR subunit vaccine may be a promising approach for immunocastration, but it still needs improvements in effectiveness.

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Use of Synthetic Peptides as Immunogens for Developing a Vaccine Against Human Chorionic Gonadotropin

Stevens

2007

Novartis Foundation Symposia

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Effects of Immunization with the β-Subunit of Ovine Luteinizing Hormone on Corpus Luteum Function in the Rhesus Monkey

Cited by 46 publications

References 8 publications

A vaccine that prevents pregnancy in women.

A vaccine that prevents pregnancy in women.

Effects of Vaccination against Recombinant FSH or LH Receptor Subunits on Gonadal Development and Functioning Male Rats

Use of Synthetic Peptides as Immunogens for Developing a Vaccine Against Human Chorionic Gonadotropin

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