title: Novel human SR-BI antibodies prevent infection and dissemination of HCV in vitro and in humanized mice.
abstract: OBJECTIVE
  Hepatitis C virus (HCV)-induced end-stage liver disease is currently the major indication for liver transplantation in the Western world. After transplantation, the donor liver almost inevitably becomes infected by the circulating virus and disease progression is accelerated in immune suppressed transplant patients. The current standard therapy, based on pegylated interferon and ribavirin, induces severe side effects and is often ineffective in this population. Therefore, new strategies to prevent graft re-infection are urgently needed. We have previously shown that monoclonal antibodies (mAbs) against the HCV co-receptor scavenger receptor class B type I (SR-BI/Cla1) inhibit infection by different HCV genotypes in cell culture.
  
  
  METHODS
  Using phage display libraries, we have generated a large set of novel human mAbs against SR-BI and evaluated their effectiveness in preventing HCV infection and direct cell-to-cell spread in vitro and in vivo using uPA-SCID mice with a humanized liver.
  
  
  RESULTS
  Eleven human monoclonal antibodies were generated that specifically recognize SR-BI. Two antibodies, mAb8 and mAb151, displayed the highest binding and inhibitory properties and also interfered with direct cell-to-cell spread in vitro. Studies in humanized mice showed that both antibodies were capable of preventing HCV infection and could block intrahepatic spread and virus amplification when administered 3 days after infection. Interestingly, anti-SR-BI therapy was effective against an HCV variant that escaped the control of the adaptive immune response in a liver transplant patient.
  
  
  CONCLUSIONS
  The anti-SR-BI mAbs generated in this study may represent novel therapeutic tools to prevent HCV re-infection of liver allografts.
authors.affiliation: CEINGE, Naples, Italy.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Lacek
authors.forename: Koen
authors.initials: K
authors.lastname: Vercauteren
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Grzyb
authors.forename: Mariarosaria
authors.initials: M
authors.lastname: Naddeo
authors.forename: Lieven
authors.initials: L
authors.lastname: Verhoye
authors.forename: Marek Patryk
authors.initials: MP
authors.lastname: Słowikowski
authors.forename: Samira
authors.initials: S
authors.lastname: Fafi-Kremer
authors.forename: Arvind H
authors.initials: AH
authors.lastname: Patel
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Baumert
authors.forename: Antonella
authors.initials: A
authors.lastname: Folgori
authors.forename: Geert
authors.initials: G
authors.lastname: Leroux-Roels
authors.forename: Riccardo
authors.initials: R
authors.lastname: Cortese
authors.forename: Philip
authors.initials: P
authors.lastname: Meuleman
authors.forename: Alfredo
authors.initials: A
authors.lastname: Nicosia
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D016466:CHO Cells; D006224:Cricetinae; D005838:Genotype; D056945:Hep G2 Cells; D016174:Hepacivirus / Q000235:genetics / Q000254:growth & development / Q000276:immunology*; D019698:Hepatitis C, Chronic / Q000276:immunology / Q000517:prevention & control*; D022781:Hepatocytes / Q000276:immunology / Q000637:transplantation / Q000821:virology; D006801:Humans; D007074:Immunoglobulin G / Q000235:genetics / Q000276:immunology / Q000494:pharmacology; D007135:Immunoglobulin Variable Region / Q000235:genetics / Q000276:immunology / Q000494:pharmacology; D051379:Mice; D016513:Mice, SCID; D008969:Molecular Sequence Data; D019151:Peptide Library; D051122:Scavenger Receptors, Class B / Q000276:immunology*; D018183:Transplantation Chimera; D014183:Transplantation, Heterologous
chemical_list: D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D007135:Immunoglobulin Variable Region; D019151:Peptide Library; C495124:SCARB1 protein, human; D051122:Scavenger Receptors, Class B