title: Human broadly neutralizing antibodies to the envelope glycoprotein complex of hepatitis C virus.
abstract: Hepatitis C virus (HCV) infects ∼2% of the world's population. It is estimated that there are more than 500,000 new infections annually in Egypt, the country with the highest HCV prevalence. An effective vaccine would help control this expanding global health burden. HCV is highly variable, and an effective vaccine should target conserved T- and B-cell epitopes of the virus. Conserved B-cell epitopes overlapping the CD81 receptor-binding site (CD81bs) on the E2 viral envelope glycoprotein have been reported previously and provide promising vaccine targets. In this study, we isolated 73 human mAbs recognizing five distinct antigenic regions on the virus envelope glycoprotein complex E1E2 from an HCV-immune phage-display antibody library by using an exhaustive-panning strategy. Many of these mAbs were broadly neutralizing. In particular, the mAb AR4A, recognizing a discontinuous epitope outside the CD81bs on the E1E2 complex, has an exceptionally broad neutralizing activity toward diverse HCV genotypes and protects against heterologous HCV challenge in a small animal model. The mAb panel will be useful for the design and development of vaccine candidates to elicit broadly neutralizing antibodies to HCV.
authors.affiliation: Department of Immunology and Microbial Science and International AIDS Vaccine Initiative Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Erick
authors.initials: E
authors.lastname: Giang
authors.forename: Marcus
authors.initials: M
authors.lastname: Dorner
authors.forename: Jannick C
authors.initials: JC
authors.lastname: Prentoe
authors.forename: Marlène
authors.initials: M
authors.lastname: Dreux
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Evans
authors.forename: Jens
authors.initials: J
authors.lastname: Bukh
authors.forename: Charles M
authors.initials: CM
authors.lastname: Rice
authors.forename: Alexander
authors.initials: A
authors.lastname: Ploss
authors.forename: Dennis R
authors.initials: DR
authors.lastname: Burton
authors.forename: Mansun
authors.initials: M
authors.lastname: Law
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D057134:Antibodies, Neutralizing / Q000276:immunology*; D000918:Antibody Specificity / Q000276:immunology; D045744:Cell Line, Tumor; D004797:Enzyme-Linked Immunosorbent Assay; D018985:Epitopes, B-Lymphocyte / Q000276:immunology; D005838:Genotype; D057809:HEK293 Cells; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology*; D006526:Hepatitis C / Q000276:immunology / Q000517:prevention & control / Q000821:virology; D018937:Hepatitis C Antibodies / Q000276:immunology; D006801:Humans; D015151:Immunoblotting; D051379:Mice; D008969:Molecular Sequence Data; D019151:Peptide Library; D060225:Tetraspanin 28 / Q000276:immunology; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology*; D014761:Viral Hepatitis Vaccines / Q000008:administration & dosage / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; C554799:Cd81 protein, mouse; D018985:Epitopes, B-Lymphocyte; D018937:Hepatitis C Antibodies; D019151:Peptide Library; D060225:Tetraspanin 28; D014759:Viral Envelope Proteins; D014761:Viral Hepatitis Vaccines