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A Human monoclonal antibody targeting scavenger receptor class B type I precludes hepatitis C virus infection and viral spread in vitro and in vivo
Author(s) -
Meuleman Philip,
Catanese Maria Teresa,
Verhoye Lieven,
Desombere Isabelle,
Farhoudi Ali,
Jones Christopher T.,
Sheahan Timothy,
Grzyb Katarzyna,
Cortese Riccardo,
Rice Charles M.,
LerouxRoels Geert,
Nicosia Alfredo
Publication year - 2012
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.24692
Subject(s) - virology , monoclonal antibody , antibody , hepatitis c virus , biology , viremia , immunology , scavenger receptor , in vivo , liver disease , transplantation , virus , medicine , lipoprotein , biochemistry , cholesterol , microbiology and biotechnology
Endstage liver disease caused by chronic hepatitis C virus (HCV) infection is the leading indication for liver transplantation in the Western world. However, immediate reinfection of the grafted donor liver by circulating virus is inevitable and liver disease progresses much faster than the original disease. Standard antiviral therapy is not well tolerated and usually ineffective in liver transplant patients, whereas anti‐HCV immunotherapy is hampered by the extreme genetic diversity of the virus and its ability to spread by way of cell‐cell contacts. We generated a human monoclonal antibody against scavenger receptor class B type I (SR‐BI), monoclonal antibody (mAb)16‐71, which can efficiently prevent infection of Huh‐7.5 hepatoma cells and primary hepatocytes by cell‐culture‐derived HCV (HCVcc). Using an Huh7.5 coculture system we demonstrated that mAb16‐71 interferes with direct cell‐to‐cell transmission of HCV. Finally we evaluated the in vivo efficacy of mAb16‐71 in “human liver urokinase‐type plasminogen activator, severe combined immune deficiency (uPA‐SCID) mice” (chimeric mice). A 2‐week anti‐SR‐BI therapy that was initiated 1 day before viral inoculation completely protected all chimeric mice from infection with serum‐derived HCV of different genotypes. Moreover, a 9‐day postexposure therapy that was initiated 3 days after viral inoculation (when viremia was already observed in the animals) suppressed the rapid viral spread observed in untreated control animals. After cessation of anti‐SR‐BI‐specific antibody therapy, a rise of the viral load was observed. Conclusion : Using in vitro cell culture and human liver‐chimeric mouse models, we show that a human mAb targeting the HCV coreceptor SR‐BI completely prevents infection and intrahepatic spread of multiple HCV genotypes. This strategy may be an efficacious way to prevent infection of allografts following liver transplantation in chronic HCV patients, and may even hold promise for the prevention of virus rebound during or following antiviral therapy. (H EPATOLOGY 2012)