Neutralization of Hepatitis B Virus Infectivity by a Murine Monoclonal Antibody: An Experimental Study in the Chimpanzee

Abstract

Two study chimpanzees were inoculated intravenously with approximately 1,000 chimpanzee infectious doses of hepatitis B virus (HBV), one with subtype adr and one with subtype ayw, each previously incubated with 0.1 ml of a murine monoclonal antibody (IgG _1(K) class) directed against a single epitope on hepatitis B surface antigen common to most or all HBV. Two control chimpanzees received identical doses of HBV not incubated with the murine anti‐HBs. Neither study chimpanzee developed HBV infection during 12 months of follow‐up as judged by normal serum aminotransferase activity, normal liver biopsies, and negative serological tests for HBV‐associated antigens and antibodies. In contrast, both control chimpanzees became infected by HBV as evidenced by elevated serum aminotransferase activity, liver biopsy changes characteristic of viral hepatitis, and the appearance of hepatitis B surface antigen (HBsAg) in their sera. Both study chimpanzees were shown to be fully susceptible to infection with these same HBV inocula when challenged 15 months after the initial inoculations at a time when passively administered anti‐HBs was no longer detectable. Prior to challenge with HBV, one of the two study chimpanzees received a second injection of the same volume of the murine monoclonal anti‐HBs. The survival of this anti‐HBs in serum was reduced from six weeks (after the initial injection) to approximately two weeks. This study documents the biological efficacy of a murine monoclonal antibody (anti‐HBs) directed against a single epitope on HBsAg in neutralizing the infectivity of Approximately 1,000 infectious doses of either HBV subtype adr or HBV subtype ayw.