Predicting the Effectiveness of Hepatitis C Virus Neutralizing Antibodies by Bioinformatic Analysis of Conserved Epitope Residues Using Public Sequence Data

Frontiers in Immunology
Vanessa M CowtonArvind H Patel

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 conserva...Continue Reading

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Citations

Feb 29, 2020·PLoS Computational Biology·Lenka StejskalJoe Grove
Dec 20, 2018·BMC Bioinformatics·Joshua B SingerRobert J Gifford
Jan 28, 2020·Journal of Peptide Science : an Official Publication of the European Peptide Society·Theodorus J MeulemanRob M J Liskamp
Apr 18, 2019·Journal of Hepatology·Florian WrenschThomas F Baumert
Jun 3, 2021·Viruses·Itai YechezkelNetanel Tzarum

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Methods Mentioned

BETA
glycosylation
dissection
glycosylations
co-crystallization

Software Mentioned

GLUE
Genes Linked by Underlying Evolution ( GLUE )
HCV

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