Cowton, V. M., Singer, J. B., Gifford, R. J. and Patel, A. H. (2018) Predicting the effectiveness of hepatitis C virus neutralizing antibodies by bioinformatic analysis of conserved epitope residues using public sequence data. Frontiers in Immunology, 9, 1470. (doi: 10.3389/fimmu.2018.01470) (PMID:30013555) (PMCID:PMC6036255)
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Abstract
Hepatitis C virus (HCV) is a global health issue. Although direct-acting antivirals are available to target HCV, there is currently no vaccine. The diversity of the virus is a major obstacle to HCV vaccine development. One approach toward a vaccine is to utilize a strategy to elicit broadly neutralizing antibodies (bNAbs) that target highly-conserved epitopes. The conserved epitopes of bNAbs have been mapped almost exclusively to the E2 glycoprotein. In this study, we have used HCV-GLUE, a bioinformatics resource for HCV sequence data, to investigate the major epitopes targeted by well-characterized bNAbs. Here, we analyze the level of conservation of each epitope by genotype and subtype and consider the most promising bNAbs identified to date for further study as potential vaccine leads. For the most conserved epitopes, we also identify the most prevalent sequence variants in the circulating HCV population. We examine the distribution of E2 sequence data from across the globe and highlight regions with no coverage. Genotype 1 is the most prevalent genotype worldwide, but in many regions, it is not the dominant genotype. We find that the sequence conservation data is very encouraging; several bNAbs have a high level of conservation across all genotypes suggesting that it may be unnecessary to tailor vaccines according to the geographical distribution of genotypes.
| Item Type: | Articles |
|---|---|
| Additional Information: | Also funded by the Medical Research Council grant MC_UU12014/12 (RG). |
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Singer, Dr Josh and Cowton, Dr Vanessa and Gifford, Dr Robert and Patel, Professor Arvind |
| Authors: | Cowton, V. M., Singer, J. B., Gifford, R. J., and Patel, A. H. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research |
| Journal Name: | Frontiers in Immunology |
| Publisher: | Frontiers Media |
| ISSN: | 1664-3224 |
| ISSN (Online): | 1664-3224 |
| Copyright Holders: | Copyright © 2018 Cowton, Singer, Gifford and Patel |
| First Published: | First published in Frontiers in Immunology 9:1470 |
| Publisher Policy: | Reproduced in accordance with the copyright policy of the publisher |
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