Relationship between the structure and immunogenicity of ceftriaxone

Abstract

This study focused on the relationship between the chemical structure and immunogenicity of ceftriaxone. Twelve tested compounds were selected and prepared, including ceftriaxone, another member of cephalosporins with or without an identical R1 side chain as ceftriaxone, a ring nucleus of cephalosporins, R1 and R2 side chain moieties, degradation products, and octalysine conjugate. Two degradation products and an octalysine-ceftriaxone conjugate were synthesized with yield values of 53.8%, 60.5% and 4.4%, respectively. The structure and purity (greater than 95%) for all tested compounds were characterized and determined, respectively, prior to their immunogenicity evaluation. The immunogenicity was evaluated by using interferon-gamma enzyme-linked immunosorbent spot (ELISPOT IFN-γ). Peripheral blood mononuclear cells (PBMC) obtained from three subjects allergic to ceftriaxone were tested with the tested compounds. A number of IFN-γ SFC/106 PBMC greater than 2SD of the mean values in ten control subjects was defined as a positive response. The results suggested that the ring nucleus together with R1 side chain could play a role in ceftriaxone allergic response more than the ring nucleus or R1 side chain alone. We found that octalysine conjugate can enhance the ELISPOT response. However, due to limitations on our allergic sample, a greater population of PBMC, obtained from subjects allergic to ceftriaxone without other factors related to allergic reaction, is needed in further study.