title: Human monoclonal antibodies that react with the E2 glycoprotein of hepatitis C virus and possess neutralizing activity.
abstract: Active and/or passive immunoprophylaxis against hepatitis C virus (HCV) remain unachieved goals. Monoclonal antibodies might provide one approach to protection. We derived human monoclonal antibodies from the bone marrow of a patient with a well-controlled HCV infection of 22 years duration. Five distinct antibodies reactive with the E2 glycoprotein of the homologous 1a strain of HCV were recovered as antigen-binding fragments (FAbs). They demonstrated affinity constants as high as 2 nanomolar. "Neutralization of binding" titers paralleled the affinity constants. All five FAbs reacted with soluble E2 protein only in nonreducing gels, indicating that the relevant epitopes were conformational. The FAbs could be divided into two groups, based on competition analysis. Three of the FAbs neutralized the infectivity of pseudotyped virus particles (pp) bearing the envelope glycoproteins of the homologous HCV strain (genotype 1a). The three FAbs also neutralized genotype 1b pp and one also neutralized genotype 2a pp. In conclusion, one or more of these monoclonal antibodies may be useful in preventing infections by HCV belonging to genotype 1 or 2, the most medically important genotypes worldwide.
authors.affiliation: Hepatitis Viruses Section, Laboratory of Infectious Diseases, NIAID, National Institutes of Health, Bethesda, MD 20892-8009, USA.
authors.forename: Darren J
authors.initials: DJ
authors.lastname: Schofield
authors.forename: Birke
authors.initials: B
authors.lastname: Bartosch
authors.forename: Yohko K
authors.initials: YK
authors.lastname: Shimizu
authors.forename: Tobias
authors.initials: T
authors.lastname: Allander
authors.forename: Harvey J
authors.initials: HJ
authors.lastname: Alter
authors.forename: Suzanne U
authors.initials: SU
authors.lastname: Emerson
authors.forename: François-Loïc
authors.initials: FL
authors.lastname: Cosset
authors.forename: Robert H
authors.initials: RH
authors.lastname: Purcell
mesh_terms: D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000915:Antibody Affinity; D000918:Antibody Specificity; D015703:Antigens, CD / Q000276:immunology; D015153:Blotting, Western; D018604:Epitope Mapping; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000235:genetics / Q000302:isolation & purification; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D060225:Tetraspanin 28; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; C554798:CD81 protein, human; C087035:E1 protein, Hepatitis C virus; D007140:Immunoglobulin Fab Fragments; D060225:Tetraspanin 28; D014759:Viral Envelope Proteins; C091015:glycoprotein E2, Hepatitis C virus