DEVELOPMENT OF HEPATITIS C VIRUS-LIKE PARTICLES AS CANDIDATE HCV VACCINE

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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. At the present time, no vaccines to prevent infection with HCV are available and the epidemic continues unabated worldwide. The objectives of this study are to develop a candidate HCV vaccine consisting of HCV-like particles and to evaluate the immunogenicity of the vaccine in the chimpanzee model. HCV subtypes 1b and 1a are being titrate in four chimpanzees to provide a standardized inoculum for vaccine challenge dose. Of the three animals inoculated with subtype 1b, one has resisted infection, and the remaining two have developed chronic infections. T cell responses in all three animals are being evaluated to understand the difference in the outcome of the infection and to delineate the role of T cells in protective immunity against HCV infection. The remaining animal has been inoculated with subtype 1a and is being monitored for evidence of infection. Two chronically infected animals are being utilized to determine whether a pool of human monoclonal anti-HCV antibodies is capable of clearing chronic infection. The animals were treated with 5 mg/kg dose of the antibody preparation and their virological and immunological status are being monitored. An additional four HCV na¿ve chimpanzees were immunized with HCV-VLP vaccine formulated with adjuvants and immunostimulatory complexes. The vaccinated animals have been challenged with infectious HCV to determine the efficacy of the vaccine preventing infection.