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영어

Hepatitis B virus (HBV) is one of the main pathogens responsible for hepatitis and hepatocellular carcinoma. Human plasma-derived hepatitis B immune globulin (HBIG) is being used for prophylactic and liver transplantation currently. However, it may be necessary to replace a HBIG with a recombinant one because of limited availability of human plasma with high anti-HBs antibody titer. In order to meet these requirements, we developed a recombinant HBIG (rHBIG) using antibody engineering technologies. The activity of rHBIG is much higher than that of HBIG from human plasma; 3,500 vs 10 units/mg. The rHBIG does not bind to normal human tissues examined, although it binds to HBV-infected human liver tissue. Neutralization of the HBV by rHBIG was proved in a chimpanzee model where the rHBIG treated chimpanzees did not show any signs of HBV infection during one year of follow up. We also demonstrated that this rHBIG is able to neutralize G145R mutant of the HBV in a hydrodynamic mouse model; the G145R mutant is a typical mutant known to escape from HBIG treatment. We identified that the rHBIG recognizes strictly conserved amino acid residues of HBsAg, which plays a key role in neutralizing the diverse HBV mutants. Safety of the rHBIG was proved in monkeys. In healthy human volunteers, the rHBIG was well tolerated without any serious adverse events up to 8 folds of clinical dose and current stage is in clinical phase II/III for liver transplantation in Korea. Further we plan to apply this rHBIG to chronic hepatitis treatment caused by HBV with combination of a current polymerase inhibitor. This rHBIG has several advantages compared to plasma-derived HBIG in activity, safety and availability.