Identification of a broadly cross-reacting and neutralizing human monoclonal antibody directed against the hepatitis C virus E2 protein

M Perotti, N Mancini, RA Diotti, AW Tarr, JK Ball… - Journal of …, 2008 - Am Soc Microbiol
M Perotti, N Mancini, RA Diotti, AW Tarr, JK Ball, A Owsianka, R Adair, AH Patel, M Clementi
Journal of virology, 2008Am Soc Microbiol
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 …
Abstract
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.
American Society for Microbiology