Elimination of luteinizing hormone cross-reactive epitopes from human chorionic gonadotropin.

Porakishvili, Nino, Chiesa, Marta Dalla, Chikadze, Nino, Martensen, Pia M., Justesen, Just, Lund, Torben, Delves, Peter J. and Roitt, Ivan (2002) Elimination of luteinizing hormone cross-reactive epitopes from human chorionic gonadotropin. Vaccine, 20 (16) . pp. 2053-2059. ISSN 0264-410X [Article] (doi:10.1016/S0264-410X(02)00051-8)

Abstract

The β-chain of human chorionic gonadotropin (hCG) has been shown to have efficacy in clinical trials when used as a contraceptive vaccine. This hormone is a heterodimer, the α-chain being shared with the other members of the glycoprotein hormone family but the β-chain being unique to hCG. Nevertheless, there is sequence homology between the hCG β-chain and the β-chain of human luteinizing hormone (hLH) which results in cross-reactive antibodies being produced following immunization with wild-type hCGβ. To reduce or eliminate such cross-reactions we generated a number of mutants of the hCGβ-chain. One mutant (hCGβ(R68E)), containing an arginine to glutamic acid replacement at position 68, has been expressed as a recombinant protein in High Five™ insect cells. The recombinant BAChCGβ(R68E) form of this molecule was used to immunize rabbits and the antibody response compared to the response following immunization with the recombinant wild-type protein BAChCGβ and with the native hCGαβ heterodimer isolated from pregnancy urine. The mutant elicited the production of antibodies which avidly recognize native hCG. Compared to immunization with wild-type hCG, the response showed very little cross reactivity with hLH. This is demonstrated to be due to a radically altered epitope usage in the response to the mutant, which now focuses mainly upon the C-terminal region of the β-chain.

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