IMPACT OF HUMAN MAB AGAINST HCV E2 SURFACE GLYCOPROTIEN ON HCV INFECTION

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Hepatitis C infection is the leading cause of liver transplantation in the United States and there is an urgent need to develop therapy aimed to reduce rates of re-infection of transplanted livers. The sponsor of this study has developed a fully human monoclonal antibody directed at a linear epitope of the HCV E2 glycoprotein and has shown that this monoclonal antibody effectively neutralizes pseudovirus from HCV genotypes 1a, 1b, 2b, 3a, and 4a, and replication competent HCV in a cell culture assay using HCVcc strain JFH1/J6. Based on these in vitro results, a study was conducted to demonstrate the ability of the monoclonal to prevent HCV infection in uninfected chimpanzees. Three chimpanzees were studied and received either 0mg/kg, 50mg/kg, or 250mg/kg of antibody intravenously approximately 30 minutes prior to challenge with 32 Chimpanzee Infectious Doses (CID) of HCV strain H77. The animals were followed for 20 weeks with weekly PCR based viral load analysis as well as clinical and laboratory safety assessments. The lower limit of quantification of viral RNA was 500 Genomes/mL (Ge/mL).