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

Mario Perotti, Nicasio Mancini, Roberta A. Diotti, Alexander W. Tarr, Jonathan K. Ball, Ania Owsianka, R. Adair, Arvind H. Patel, Massimo Clementi, Roberto Burioni

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)1047-1052
Number of pages6
JournalJournal of Virology
Volume82
Issue number2
DOIs
Publication statusPublished - Jan 2008

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Hepatitis C virus
neutralization
Hepacivirus
monoclonal antibodies
Genotype
Monoclonal Antibodies
genotype
Proteins
proteins
Forensic Anthropology
antibodies
Hepatitis C Antibodies
Passive Immunization
immunotherapy
Mutant Proteins
Neutralizing Antibodies
neutralizing antibodies
Alanine
alanine
epitopes

ASJC Scopus subject areas

  • Immunology

Cite this

Identification of a broadly cross-reacting and neutralizing human monoclonal antibody directed against the hepatitis C virus E2 protein. / Perotti, Mario; Mancini, Nicasio; Diotti, Roberta A.; Tarr, Alexander W.; Ball, Jonathan K.; Owsianka, Ania; Adair, R.; Patel, Arvind H.; Clementi, Massimo; Burioni, Roberto.

In: Journal of Virology, Vol. 82, No. 2, 01.2008, p. 1047-1052.

Research output: Contribution to journalArticle

Perotti, Mario ; Mancini, Nicasio ; Diotti, Roberta A. ; Tarr, Alexander W. ; Ball, Jonathan K. ; Owsianka, Ania ; Adair, R. ; Patel, Arvind H. ; Clementi, Massimo ; Burioni, Roberto. / Identification of a broadly cross-reacting and neutralizing human monoclonal antibody directed against the hepatitis C virus E2 protein. In: Journal of Virology. 2008 ; Vol. 82, No. 2. pp. 1047-1052.
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