Biomedical subjects

P T Koothan

Publications and source records attributed to P T Koothan.

4 recordsLinked to original sources

PubMed1993

Contraceptive vaccines.

Three major approaches to contraceptive vaccine development are being pursued at the present time. The most advanced approach, which has already reached the stage of phase 2 clinical trials, involves the induction of immunity against human chorionic gonadotrophin (hCG). Vaccines are being engineered based on conjugates incorporating tetanus or diphtheria toxoid linked to a variety of hCG-based peptides centred on the beta-subunit of this molecule. Clinical trials have revealed that such preparations are capable of stimulating the production of anti-hCG antibodies. However, the long term consequences of such immunity in terms of safety or efficacy are, as yet, unknown. The alternative approaches to contraceptive vaccine development involve the induction of immunity against gamete-specific antigens found on the surface of the human spermatozoon or the zona pellucida. There is an abundance of experimental and clinical data to suggest that this approach is feasible although the biochemical characterization and synthesis of candidate antigens is still incomplete.

Animals↗

PubMed1992

Analysis of the contraceptive potential of antibodies against native and deglycosylated porcine ZP3 in vivo and in vitro.

We have undertaken a comparative analysis of the contraceptive activity of antibodies directed against the porcine sperm receptor zona pellucida antigen (ZP3) and its Mr = 32,000 polypeptide core (DGZP-32). The strategies employed for this analysis included the induction of active immunity in a primate, the common marmoset, and an in vitro fertilization protocol involving the use of viable human ova. In both experimental situations, antibodies against ZP3 were shown to exhibit contraceptive activity, leading respectively to the induction of long-term infertility in the primate model and to the complete inhibition of human fertilization in vitro. The in vivo studies also revealed that the induction of high titer antibodies against ZP3 was inevitably associated with the appearance of an ovarian pathology characterized by the progressive depletion of the primordial follicle pool within one to two years. This side effect could not be alleviated by the use of DGZP-32 as antigen since the induction of immunity against this polypeptide was also associated with the eventual appearance of an ovarian pathology identical to that observed with ZP3. Furthermore, the DGZP-32 peptide was less effective than ZP3 in inducing the formation of antibodies capable of inhibiting the fertilization of human ova in vitro. We conclude that significant problems remain with the use of deglycosylated zona peptides for the development of contraceptive vaccines and that their potential will not be realized until the epitopes responsible for the induction of infertility and the primordial follicle depletion have been identified and segregated.

Animals↗

PubMed1992

Characteristics of monoclonal antibodies against porcine zona pellucida-3 and their functional relevance.

Seven monoclonal antibodies (MAs) against 55 kDa glycoprotein family of porcine zona pellucida (ZP3) reacting with either ZP3 alpha (MA-7, MA-27, MA-28) or ZP3 beta (MA-1, MA-2, MA-11, MA-30) have been described. MA-1, -2, -27, -28 and -30 do not recognize carbohydrate determinants as shown by their reactivity to the deglycosylated (DG) ZP3 alpha and ZP3 beta. Indirect immunoperoxidase studies showed that all MAs reacted with zona pellucida from porcine and monkey ovaries. Only MA-1 and -27 reacted with ZP from rabbit ovary as well, while none of the MAs recognised mouse ZP, MA-7, -11, -27, -28 and -30 inhibited in vitro, the zona lysis by trypsin as well as the binding of ZP3 to sperm membrane vesicle as investigated by ELISA.

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↗