FUNCTIONAL AND IMMUNOLOGICAL RELEVANCE OF THE COOH-TERMINAL EXTENSION OF HUMAN CHORIONIC GONADOTROPIN-BETA - IMPLICATIONS FOR THE WHO BIRTH-CONTROL VACCINE

The World Health Organisation (WHO) Task Force on Birth Control Vaccines has selected the pregnancy hormone human chorionic gonadotropin (hCG) as a target molecule for a contraceptive vaccine. A synthetic peptide antigen corresponding to the amino acid sequence 109-145 of the carboxyl-terminal portion of the hCGbeta-subunit (hCGbetaCTP), which is supposed to elicit hCG-immunoneutralizing antibodies, has been submitted to clinical trails. Recent findings suggest that hCGbetaCTP does not play a role in the biological activity of hCG. This raises the question concerning the assumed mechanism of action of the hCGbetaCTP-based birth control vaccine. We therefore investigated the immunoneutralizing capacity of antibodies directed against hCGbetaCTP. Although it is possible to generate specific monoclonal and polyclonal antibodies for hCG by using hCGbetaCTP as an immunogen, it appeared that the biological response to hCG was not affected by such antibodies. The reason for this is that the hCG-antibody-complex is still able to bind to target cell receptors and therefore the intended contraceptive effect should not occur. In addition there is a risk of hazardous possible side effects such as an autoimmune reaction against the ovary because we found that at least one epitope is still accessible for antibody binding on receptor-bound hCG. We conclude from our results that both the efficacy and safety of the WHO vaccine are not yet ensured.