In vivo inhibition of hepatitis C virus infection by anti‐Claudin‐1 monoclonal antibodies (1062.9)

More than 170 million people worldwide are infected with hepatitis C virus (HCV). Despite concerted research efforts, anti‐HCV agents resistant to the high mutability of the HCV RNA genome have not yet been produced. Claudin 1 (CLDN1) is a co‐receptor for HCV entry into hepatocytes and is an attractive potential target for HCV therapy, because such host factors are genetically stable. Here, we investigated the effects of 4 previously generated mouse anti‐CLDN1 antibodies on HCV infection. All 4 clones attenuated the infection of Huh7 cells by HCV (genotype 2a) and HCV pseudoviral particles (HCVpp, genotypes 1b and 2a). Two of 4 clones also prevented HCV (genotype 1b) infection of human‐liver‐chimeric mice. Injection of mouse anti‐CLDN1 antibodies did not adversely affect serum human albumin levels, apparent character, and motility. For future clinical application, we prepared human‐mouse chimeric anti‐CLDN1 antibodies. The chimeric antibodies prevented HCV and HCVpp infection of Huh7 cells as effectively as did the mouse antibodies. Our findings suggest that mouse and mouse‐human chimeric anti‐CLDN1 antibodies prevent HCV infection and may therefore be promising candidate anti‐HCV agents. Grant Funding Source : supported by the Ministry of Health, Labor, and Welfare of Japan