Comparison of the immunogenicity of a mutant recombinant hCGβ-protein conjugated to different carrier molecules

Author: Nino Gachechiladze
Co-authors: Chikadze N, Mitskevich N, Gachechiladze N
Keywords: hCG, KLH, CTP
Annotation:

Human chorionic gonadotropin (hCG) is a heterodimeric hormone consisting of an α chain, shared with other glycoprotein hormones, and an hCG-specific β-chain. Since hCG is instrumental in the early maintenance of pregnancy, and is an important tumor growth factor, the hormones and its components have been a target for a development of immunocontraceptive and anti-cancer vaccines. We have constructed three prototypes of anti-hCG vaccines based upon the recombinant hCG β-chain (hCGβ) with a single point mutation of arginine68 to glutamic acid [hCGβ(R68E)]. In two of them hCGβ(R68E) has been conjugated to heat shock protein 70 (hCGβ(R68E)-HSP70) or to keyhole limpet hemocyanin (hCGβ(R68E)-KLH) as carrier molecules , and the third contained hCGβ(R68E) alone. Mice were immunized with these preparations, and specificity and immunogenicity of the sera against native hCGαβ, hCGβ-chain and C-terminal peptide of hCGβ (CTP) was studied using a direct binding ELISA. All three preparations induced appreciable antibody immune responses to the proteins studied. However whilst hCGβ(R68E)-KLH and hCGβ(R68E) alone elicited high titers of anti-CTP antibodies, the sera reacted weaker with the native hCG. In contrast, the anti- hCGβ(R68E)-HSP70 sera contained high titers of anti-CTP, anti-hCGαβ and anti-hCGβ antibodies. Our data argues in favor of the effectiveness of hCGβ(R68E)-HSP70 for a vaccine formulation.