Human broadly neutralizing antibodies to the envelope glycoprotein complex of hepatitis C virus

Erick Giang, Marcus Dorner, Jannick C. Prentoe, Marlène Dreux, Matthew J. Evans, Jens Bukh, Charles M. Rice, Alexander Ploss, Dennis R. Burton, Mansun Law

Research output: Contribution to journalArticle

221 Scopus citations

Abstract

Hepatitis C virus (HCV) infects ∼2% of the world's population. It is estimated that there are more than 500,000 new infections annually in Egypt, the country with the highest HCV prevalence. An effective vaccine would help control this expanding global health burden. HCV is highly variable, and an effective vaccine should target conserved T- and B-cell epitopes of the virus. Conserved B-cell epitopes overlapping the CD81 receptor-binding site (CD81bs) on the E2 viral envelope glycoprotein have been reported previously and provide promising vaccine targets. In this study, we isolated 73 human mAbs recognizing five distinct antigenic regions on the virus envelope glycoprotein complex E1E2 from an HCV-immune phage-display antibody library by using an exhaustive-panning strategy. Many of these mAbs were broadly neutralizing. In particular, the mAb AR4A, recognizing a discontinuous epitope outside the CD81bs on the E1E2 complex, has an exceptionally broad neutralizing activity toward diverse HCV genotypes and protects against heterologous HCV challenge in a small animal model. The mAb panel will be useful for the design and development of vaccine candidates to elicit broadly neutralizing antibodies to HCV.

Original languageEnglish (US)
Pages (from-to)6205-6210
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume109
Issue number16
DOIs
StatePublished - Apr 17 2012
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • General

Keywords

  • Antigenic determinant
  • Chronic viral infection
  • Cross-neutralizing antibody
  • Protective determinant
  • Virus challenge

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