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Polyclonal immunoglobulins from a chronic hepatitis C virus patient protect human liver–chimeric mice from infection with a homologous hepatitis C virus strain
Author(s) -
Vanwolleghem Thomas,
Bukh Jens,
Meuleman Philip,
Desombere Isabelle,
Meunier JeanChristophe,
Alter Harvey,
Purcell Robert H.,
LerouxRoels Geert
Publication year - 2008
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.22244
Subject(s) - virology , viremia , antibody , polyclonal antibodies , immunology , immunoglobulin g , immune system , biology , hepatitis c virus , virus , neutralizing antibody , in vivo , medicine , microbiology and biotechnology
The role of the humoral immune response in the natural course of hepatitis C virus (HCV) infection is widely debated. Most chronically infected patients have immunoglobulin G (IgG) antibodies capable of neutralizing HCV pseudoparticles (HCVpp) in vitro . It is, however, not clear whether these IgG can prevent a de novo HCV infection in vivo and contribute to the control of viremia in infected individuals. We addressed this question with homologous in vivo protection studies in human liver–urokinase‐type plasminogen activator (uPA) +/+ severe combined immune deficient (SCID) mice. Chimeric mice were loaded with chronic phase polyclonal IgG and challenged 3 days later with a 100% infectious dose of the acute phase H77C virus, both originating from patient H. Passive immunization induced sterilizing immunity in five of eight challenged animals. In the three nonprotected animals, the HCV infection was attenuated, as evidenced by altered viral kinetics in comparison with five control IgG‐treated animals. Plasma samples obtained from the mice at viral challenge neutralized H77C‐HCVpp at dilutions as high as 1/400. Infection was completely prevented when, before administration to naïve chimeric mice, the inoculum was pre‐incubated in vitro at an IgG concentration normally observed in humans. Conclusion: Polyclonal IgG from a patient with a long‐standing HCV infection not only displays neutralizing activity in vitro using the HCVpp system, but also conveys sterilizing immunity toward the ancestral HCV strain in vivo , using the human liver–chimeric mouse model. Both experimental systems will be useful tools to identify neutralizing antibodies for future clinical use. (H EPATOLOGY 2008.)