Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 109, Issue 16, Pages 6205-6210Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1114927109
Keywords
cross-neutralizing antibody; antigenic determinant; protective determinant; chronic viral infection; virus challenge
Categories
Funding
- National Institutes of Health [R21AI080916, R01AI079031, R01AI071084, RC1DK087193, R01AI072613, R01AI079043]
- Starr Foundation
- Greenberg Medical Institute
- Center for Translational Science Award [UL1 RR024143]
- Lundbeck Foundation
- German Research Foundation (Deutsche Forschungsgesellschaft)
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Hepatitis C virus (HCV) infects similar to 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.
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