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

The World Health Organisation (WHO) Task Force on Birth Control Vaccin es has selected the pregnancy hormone human chorionic gonadotropin (hC G) as a target molecule for a contraceptive vaccine. A synthetic pepti de antigen corresponding to the amino acid sequence 109-145 of the car boxyl-terminal portion of the hCGbeta-subunit (hCGbetaCTP), which is s upposed to elicit hCG-immunoneutralizing antibodies, has been submitte d to clinical trails. Recent findings suggest that hCGbetaCTP does not play a role in the biological activity of hCG. This raises the questi on concerning the assumed mechanism of action of the hCGbetaCTP-based birth control vaccine. We therefore investigated the immunoneutralizin g capacity of antibodies directed against hCGbetaCTP. Although it is p ossible to generate specific monoclonal and polyclonal antibodies for hCG by using hCGbetaCTP as an immunogen, it appeared that the biologic al 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 eff ects 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 effica cy and safety of the WHO vaccine are not yet ensured.