Development of a structural epitope mimic: an idiotypic approach to HCV vaccine design
Open Access
- 8 January 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in npj Vaccines
- Vol. 6 (1), 1-10
- https://doi.org/10.1038/s41541-020-00269-1
Abstract
HCV vaccine development is stymied by the high genetic diversity of the virus and the variability of the envelope glycoproteins. One strategy to overcome this is to identify conserved, functionally important regions—such as the epitopes of broadly neutralizing antibodies (bNAbs)—and use these as a basis for structure-based vaccine design. Here, we report an anti-idiotype approach that has generated an antibody that mimics a highly conserved neutralizing epitope on HCV E2. Crucially, a mutagenesis screen was used to identify the antibody, designated B2.1 A, whose binding characteristics to the bNAb AP33 closely resemble those of the original antigen. Protein crystallography confirmed that B2.1 A is a structural mimic of the AP33 epitope. When used as an immunogen B2.1 A induced antibodies that recognized the same epitope and E2 residues as AP33 and most importantly protected against HCV challenge in a mouse model.This publication has 72 references indexed in Scilit:
- BeAtMuSiC: prediction of changes in protein–protein binding affinity on mutationsNucleic Acids Research, 2013
- Structural basis of hepatitis C virus neutralization by broadly neutralizing antibody HCV1Proceedings of the National Academy of Sciences of the United States of America, 2012
- A genetically humanized mouse model for hepatitis C virus infectionNature, 2011
- Rational antibody-based HIV-1 vaccine design: current approaches and future directionsCurrent Opinion in Immunology, 2010
- PHENIX: a comprehensive Python-based system for macromolecular structure solutionActa crystallographica. Section D, Structural biology, 2010
- MolProbity: all-atom structure validation for macromolecular crystallographyActa crystallographica. Section D, Structural biology, 2009
- Inference of Macromolecular Assemblies from Crystalline StateJournal of Molecular Biology, 2007
- Phasercrystallographic softwareJournal of Applied Crystallography, 2007
- Scaling and assessment of data qualityActa crystallographica. Section D, Structural biology, 2005
- Immunology of hepatitis B virus and hepatitis C virus infectionNature Reviews Immunology, 2005