Identification of a broadly cross-reacting and neutralizing human monoclonal antibody directed against the hepatitis C virus E2 protein.
Identification of anti-hepatitis C virus (anti-HCV) human antibody clones with broad neutralizing activity is important for a better understanding of the interplay between the virus and host and for the design of an effective passive immunotherapy and an effective vaccine. We report the identification of a human monoclonal Fab (e137) able to bind the HCV E2 glycoprotein of all HCV genotypes but genotype 5. The results of antibody competition assays and testing the reactivity to alanine mutant E2 proteins confirmed that the e137 epitope includes residues (T416, W420, W529, G530, and D535) highly conserved across all HCV genotypes. Fab e137 neutralized HCV pseudoparticles bearing genotype 1a, 1b, and 4 E1-E2 proteins and to a lesser extent, genotype 2b. Fab e137 was also able to inhibit cell culture-grown HCV (genotype 2a). These data indicate that broadly cross-reacting and cross-neutralizing antibodies are generated during HCV infection.
Perotti
Mario
M
Laboratorio di Microbiologia e Virologia, Università "Vita-Salute" San Raffaele, DIBIT2, via Olgettina 60, 20132 Milano, Italia. mario.perotti@hsr.it
Mancini
Nicasio
N
Diotti
Roberta A
RA
Tarr
Alexander W
AW
Ball
Jonathan K
JK
Owsianka
Ania
A
Adair
R
R
Patel
Arvind H
AH
Clementi
Massimo
M
Burioni
Roberto
R
D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000302:isolation & purification; D003429:Cross Reactions; D018604:Epitope Mapping; D016174:Hepacivirus / Q000276:immunology*; D018937:Hepatitis C Antibodies / Q000276:immunology* / Q000302:isolation & purification; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000276:immunology / Q000302:isolation & purification; D009500:Neutralization Tests; D014759:Viral Envelope Proteins / Q000276:immunology*
D000911:Antibodies, Monoclonal; D018937:Hepatitis C Antibodies; D007140:Immunoglobulin Fab Fragments; D014759:Viral Envelope Proteins; C091015:glycoprotein E2, Hepatitis C virus