An alpaca nanobody inhibits hepatitis C virus entry and cell-to-cell transmission.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
AuthorsTarr, Alexander W
Urbanowicz, Richard A
Brown, Richard J P
McKeating, Jane A
Rey, Felix A
Ball, Jonathan K
MetadataShow full item record
AbstractSevere liver disease caused by chronic hepatitis C virus is the major indication for liver transplantation. Despite recent advances in antiviral therapy, drug toxicity and unwanted side effects render effective treatment in liver-transplanted patients a challenging task. Virus-specific therapeutic antibodies are generally safe and well-tolerated, but their potential in preventing and treating hepatitis C virus (HCV) infection has not yet been realized due to a variety of issues, not least high production costs and virus variability. Heavy-chain antibodies or nanobodies, produced by camelids, represent an exciting antiviral approach; they can target novel highly conserved epitopes that are inaccessible to normal antibodies, and they are also easy to manipulate and produce. We isolated four distinct nanobodies from a phage-display library generated from an alpaca immunized with HCV E2 glycoprotein. One of them, nanobody D03, recognized a novel epitope overlapping with the epitopes of several broadly neutralizing human monoclonal antibodies. Its crystal structure revealed a long complementarity determining region (CD3) folding over part of the framework that, in conventional antibodies, forms the interface between heavy and light chain. D03 neutralized a panel of retroviral particles pseudotyped with HCV glycoproteins from six genotypes and authentic cell culture-derived particles by interfering with the E2-CD81 interaction. In contrast to some of the most broadly neutralizing human anti-E2 monoclonal antibodies, D03 efficiently inhibited HCV cell-to-cell transmission. Conclusion: This is the first description of a potent and broadly neutralizing HCV-specific nanobody representing a significant advance that will lead to future development of novel entry inhibitors for the treatment and prevention of HCV infection and help our understanding of HCV cell-to-cell transmission.
CitationAn alpaca nanobody inhibits hepatitis C virus entry and cell-to-cell transmission. 2013, 58 (3):932-9 Hepatology
AffiliationSchool of Molecular Medical Sciences, The University of Nottingham, Queen's Medical Centre, Nottingham, United Kingdom.
JournalHepatology (Baltimore, Md.)
The following license files are associated with this item:
- Human monoclonal antibodies to a novel cluster of conformational epitopes on HCV E2 with resistance to neutralization escape in a genotype 2a isolate.
- Authors: Keck ZY, Xia J, Wang Y, Wang W, Krey T, Prentoe J, Carlsen T, Li AY, Patel AH, Lemon SM, Bukh J, Rey FA, Foung SK
- Issue date: 2012
- A novel neutralizing human monoclonal antibody broadly abrogates hepatitis C virus infection in vitro and in vivo.
- Authors: Desombere I, Mesalam AA, Urbanowicz RA, Van Houtte F, Verhoye L, Keck ZY, Farhoudi A, Vercauteren K, Weening KE, Baumert TF, Patel AH, Foung SKH, Ball J, Leroux-Roels G, Meuleman P
- Issue date: 2017 Dec
- Human combinatorial libraries yield rare antibodies that broadly neutralize hepatitis C virus.
- Authors: Johansson DX, Voisset C, Tarr AW, Aung M, Ball JK, Dubuisson J, Persson MA
- Issue date: 2007 Oct 9
- Identification of a novel epitope in the C terminus of hepatitis C virus-E2 protein that induces potent and cross-reactive neutralizing antibodies.
- Authors: Das S, Mullick R, Kumar A, Tandon H, Bose M, Gouthamchandra K, Chandra M, Ravishankar B, Khaja MN, Srinivasan N, Das S, Melkote Subbarao S, Karande AA
- Issue date: 2017 May
- Combination of neutralizing monoclonal antibodies against Hepatitis C virus E2 protein effectively blocks virus infection.
- Authors: Bose M, Mullick R, Das S, Das S, Karande AA
- Issue date: 2016 Sep 15