title: Hepatitis C virus (HCV) infection may elicit neutralizing antibodies targeting epitopes conserved in all viral genotypes.
abstract: Anti-hepatitis C virus (HCV) cross-neutralizing human monoclonal antibodies, directed against conserved epitopes on surface E2 glycoprotein, are central tools for understanding virus-host interplay, and for planning strategies for prevention and treatment of this infection. Recently, we developed a research aimed at identifying these antibody specificities. The characteristics of one of these antibodies (Fab e20) were addressed in this study. Firstly, using immunofluorescence and FACS analysis of cells expressing envelope HCV glycoproteins, Fab e20 was able to recognize all HCV genotypes. Secondly, competition assays with a panel of mouse and rat monoclonals, and alanine scanning mutagenesis analyses located the e20 epitope within the CD81 binding site, documenting that three highly conserved HCV/E2 residues (W529, G530 and D535) are critical for e20 binding. Finally, a strong neutralizing activity against HCV pseudoparticles (HCVpp) incorporating envelope glycoproteins of genotypes 1a, 1b, 2a, 2b and 4, and against the cell culture-grown (HCVcc) JFH1 strain, was observed. The data highlight that neutralizing antibodies against HCV epitopes present in all HCV genotypes are elicited during natural infection. Their availability may open new avenues to the understanding of HCV persistence and to the development of strategies for the immune control of this infection.
authors.affiliation: Laboratorio di Microbiologia e Virologia, Università Vita-Salute San Raffaele, Milano, Italia. mancini.nicasio@hsr.it
authors.forename: Nicasio
authors.initials: N
authors.lastname: Mancini
authors.forename: Roberta A
authors.initials: RA
authors.lastname: Diotti
authors.forename: Mario
authors.initials: M
authors.lastname: Perotti
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Sautto
authors.forename: Nicola
authors.initials: N
authors.lastname: Clementi
authors.forename: Giovanni
authors.initials: G
authors.lastname: Nitti
authors.forename: Arvind H
authors.initials: AH
authors.lastname: Patel
authors.forename: Jonathan K
authors.initials: JK
authors.lastname: Ball
authors.forename: Massimo
authors.initials: M
authors.lastname: Clementi
authors.forename: Roberto
authors.initials: R
authors.lastname: Burioni
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D057134:Antibodies, Neutralizing / Q000276:immunology*; D000914:Antibodies, Viral / Q000276:immunology; D017124:Conserved Sequence; D000939:Epitopes / Q000737:chemistry* / Q000276:immunology*; D016174:Hepacivirus / Q000235:genetics* / Q000276:immunology*; D006526:Hepatitis C / Q000276:immunology* / Q000821:virology*; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D051381:Rats
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D000939:Epitopes; D007140:Immunoglobulin Fab Fragments