title: Neutralizing antibodies to hepatitis C virus (HCV) in immune globulins derived from anti-HCV-positive plasma.
abstract: The role of humoral immunity in hepatitis C virus (HCV) infections is uncertain. Nevertheless, there is increasing evidence for neutralizing antibodies to HCV in the serum or plasma of chronically infected individuals. Immune globulins prepared by ethanol fractionation of plasma had long been considered safe until a commercial immune globulin product, Gammagard, prepared from plasma from which units containing anti-HCV had been excluded, transmitted HCV to recipients. Studies suggested that the exclusion might have removed neutralizing antibodies from the plasma and hence compromised the safety of the resulting immune globulins. In the present study, by using chimpanzees and a recently validated in vitro system based on neutralization of infectious HCV pseudoparticles, we found broadly reactive neutralizing and protective antibodies in experimental immune globulin preparations made from anti-HCV-positive donations. Neutralizing antibodies were also found in Gammagard lots made from unscreened plasma that did not transmit hepatitis C but not in Gammagard lots, which were prepared from anti-HCV-screened plasma, that did transmit hepatitis C. The results provide an explanation for the mechanism by which the safety of this product was compromised. Immune globulins made from anti-HCV-positive plasma and containing broadly reactive neutralizing antibodies may provide a method of preventing HCV infection.
authors.affiliation: Division of Hematology, Center for Biologics Evaluation and Research, Food and Drug Administration, 29 Lincoln Drive, Bethesda, MD 20892, USA. yu@cber.fda.gov
authors.forename: Mei-ying W
authors.initials: MY
authors.lastname: Yu
authors.forename: Birke
authors.initials: B
authors.lastname: Bartosch
authors.forename: Pei
authors.initials: P
authors.lastname: Zhang
authors.forename: Zheng-ping
authors.initials: ZP
authors.lastname: Guo
authors.forename: Paula M
authors.initials: PM
authors.lastname: Renzi
authors.forename: Li-Ming
authors.initials: LM
authors.lastname: Shen
authors.forename: Christelle
authors.initials: C
authors.lastname: Granier
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Feinstone
authors.forename: François-Loïc
authors.initials: FL
authors.lastname: Cosset
authors.forename: Robert H
authors.initials: RH
authors.lastname: Purcell
mesh_terms: D000818:Animals; D001681:Biological Assay; D016174:Hepacivirus / Q000276:immunology*; D006526:Hepatitis C / Q000276:immunology / Q000517:prevention & control*; D018937:Hepatitis C Antibodies / Q000097:blood / Q000276:immunology* / Q000494:pharmacology; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000097:blood / Q000276:immunology* / Q000494:pharmacology; D002679:Pan troglodytes / Q000276:immunology
chemical_list: D018937:Hepatitis C Antibodies; D016756:Immunoglobulins, Intravenous