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

Porakishvili, N., Dalla Chiesa, M., Chikadze, N., Martensen, P., Justesen, J., Lund, T., Delves, P.J. and Roitt, I.M. 2002. Elimination of luteinizing hormone cross-reactive epitopes from human chorionic gonadotropin. Vaccine. 20 (16), pp. 2053-2059.

TitleElimination of luteinizing hormone cross-reactive epitopes from human chorionic gonadotropin
AuthorsPorakishvili, N., Dalla Chiesa, M., Chikadze, N., Martensen, P., Justesen, J., Lund, T., Delves, P.J. and Roitt, I.M.
Abstract

The beta-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 alpha-chain being shared with the other members of the glycoprotein hormone family but the beta-chain being unique to hCG. Nevertheless, there is sequence homology between the hCG beta-chain and the beta-chain of human luteinizing hormone (hLH) which results in cross-reactive antibodies being produced following immunization with wild-type hCGbeta. To reduce or eliminate such cross-reactions we generated a number of mutants of the hCGbeta-chain. One mutant (hCGbeta(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 BAChCGbeta(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 BAChCGbeta and with the native hCGalphabeta 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 beta-chain.

KeywordsHuman chorionic gonadotropin, Immunocontraception, Epitope, Luteinizing hormone
JournalVaccine
Journal citation20 (16), pp. 2053-2059
ISSN0264-410X
Year15 May 2002
Digital Object Identifier (DOI)doi:10.1016/S0264-410X(02)00051-8
Publication dates
Published15 May 2002

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