Transbody against hepatitis B virus core protein inhibits hepatitis B virus replication in vitro

Hepatitis B virus (HBV) infection is one of the major causes of chronic liver diseases. The current therapeutics show limited efficacy. In the HBV life cycle, virus core antigen (HBcAg) plays important multiple roles. Blocking the pleiotropic functions of HBcAg may thus represent a promising strategy for anti-HBV replication. In this study, monoclonal antibody (MAb) against core antigen of human HBV was coupled with TAT protein transduction domain (TAT PTD) to form transbody, and the effect on virus replication was evaluated in vitro. The HBV transbody, HBcMAb-TAT PTD conjugate, recognized HBcAg and retained cell-penetrating activity in living cells. In HBV-transfected liver cell line HepG2.2.15, HBV transbody suppressed not only the extracellular HBsAg, HBeAg and HBV DNA, but also the intracellular HBsAg, HBeAg, HBcAg and HBV DNA in a dose-dependent manner. These results indicate that the transbody prepared possesses readily cell-penetrating ability and potent antiviral activity, providing a novel approach, a cell-permeable antibody against HBcAg, for the treatment of HBV infection. (C) 2015 Elsevier B.V. All rights reserved.