Key result
A mouse-human chimeric antibody derived from 8C11 was successfully constructed and expressed, demonstrating HEV antigen-binding activity and specific inhibition of p239 binding to HepG2 cells.
The successful construction of a mouse-human chimeric antibody to HEV that retains binding and neutralizing activity suggests its potential suitability for antibody therapy of hepatitis E.
Chimeric anti-HEV antibody advances preclinical work; leaves open clinical translation and efficacy trials.
Homodimers of the truncated hepatitis E virus (HEV) capsid proteins, E2 and p239, were conformed to model the dominant antigenic determinants of HEV. Using E2 as an immunogen, two neutralizing monoclonal antibodies (mAbs), namely 8C11 and 8H3, were produced. We constructed a mouse-human chimeric antibody derived from 8C11 and its expression in Chinese hamster ovary (CHO) cells. cDNAs encoding variable regions of heavy and light chains were isolated from hybridoma cells and inserted into mammalian expression vectors containing cDNA of human gamma-1 and kappa constant regions, respectively. The vectors were then cotransfected into CHO cells, and a stable cell line was established. Results from indirect enzyme-linked immunosorbent assay (ELISA) and Western blot analysis showed that the chimeric antibody was assembled correctly to the native IgG molecule and could be secreted from the cells. Similar to the original mAb, the expressed chimeric antibody displayed HEV antigen-binding activity and an enhancement effect on 8H3 binding to HEV antigen. The chimeric antibody could specifically inhibit the binding of p239 to HepG2 cells and compete with HEV IgG in positive serum by antibody-competitive ELISA. The chimeric antibody is expected to be less immunogenic in human and more suitable for antibody therapy of hepatitis E.
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Luo et al. (2007) studied Hepatitis E virus. Chimeric antibody 8C11 was evaluated on Antigen-binding activity and inhibition of p239 binding to HepG2 cells. A mouse-human chimeric antibody derived from 8C11 was successfully constructed and expressed, demonstrating HEV antigen-binding activity and specific inhibition of p239 binding to HepG2 cells.
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