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Journal of Virology, January 2008, p. 1047-1052, Vol. 82, No. 2
0022-538X/08/$08.00+0     doi:10.1128/JVI.01986-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Identification of a Broadly Cross-Reacting and Neutralizing Human Monoclonal Antibody Directed against the Hepatitis C Virus E2 Protein{triangledown}

Mario Perotti,1* Nicasio Mancini,1 Roberta A. Diotti,1 Alexander W. Tarr,2 Jonathan K. Ball,2 Ania Owsianka,3 R. Adair,3 Arvind H. Patel,3 Massimo Clementi,1 and Roberto Burioni1

Laboratorio di Microbiologia e Virologia, Università "Vita-Salute" San Raffaele, Milano, Italia,1 Institute of Infection, Immunity and Inflammation and Division of Microbiology, University of Nottingham, Queen's Medical Centre, Nottingham NG7 2UH, United Kingdom,2 MRC Virology Unit, Institute of Virology, University of Glasgow, Church Street, Glasgow G11 5JR, United Kingdom3

Received 10 September 2007/ Accepted 29 October 2007

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.

* Corresponding author. Mailing address: Laboratorio di Microbiologia e Virologia, Università "Vita-Salute" San Raffaele, DIBIT2, via Olgettina 60, 20132 Milano, Italia. Phone: 39 02 2643 4284. Fax: 39 02 2643 4288. E-mail: mario.perotti{at}hsr.it

{triangledown} Published ahead of print on 7 November 2007.

Journal of Virology, January 2008, p. 1047-1052, Vol. 82, No. 2
0022-538X/08/$08.00+0     doi:10.1128/JVI.01986-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



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