Alexander I. Mosa
Role of HVR1 sequence similarity in the cross-genotypic neutralization of HCV
Mosa, Alexander I.; AbouHaidar, Mounir G.; Urbanowicz, Richard A.; Tavis, John E.; Ball, Jonathan K.; Feld, Jordan J.
Authors
Mounir G. AbouHaidar
Richard A. Urbanowicz
John E. Tavis
JONATHAN BALL jonathan.ball@nottingham.ac.uk
Professor of Molecular Virology
Jordan J. Feld
Abstract
Despite available treatments, a prophylactic HCV vaccine is needed to achieve elimination targets. HCV vaccine development has faltered largely because the extreme diversity of the virus limits the protective breadth of vaccine elicited antibodies. It is believed that the principle neutralizing epitope in natural infection, HVR1, which is the most variable epitope in HCV, mediates humoral immune escape. So far, efforts to circumvent HVR1 interference in the induction and function of conserved targeting Ab have failed. Efforts to understand factors contributing to cross-neutralization of HVR1 variants have also been limited. Here, following mouse immunizations with two patient-derived HVR1 peptides, we observe cross-genotype neutralization of variants differing at 15/21 positions. Surprisingly, sequence similarity was not associated with cross-neutralization. It appeared neutralization sensitivity was an intrinsic feature of each variant, rather than emergent from the immunogen specific Ab response. These findings provide novel insight into HVR1-mediated immune evasion, with important implications for HCV vaccine design.
Journal Article Type | Article |
---|---|
Acceptance Date | Aug 28, 2020 |
Online Publication Date | Sep 18, 2020 |
Publication Date | Sep 18, 2020 |
Deposit Date | Jan 5, 2021 |
Publicly Available Date | Jan 6, 2021 |
Journal | Virology journal |
Electronic ISSN | 1743-422X |
Publisher | Springer Verlag |
Peer Reviewed | Peer Reviewed |
Volume | 17 |
Article Number | 140 |
DOI | https://doi.org/10.1186/s12985-020-01408-9 |
Public URL | https://nottingham-repository.worktribe.com/output/4938108 |
Publisher URL | https://virologyj.biomedcentral.com/articles/10.1186/s12985-020-01408-9 |
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Role of HVR1 sequence
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