Journal article
Anti-Hepatitis C virus T-Cell immunity in the context of multiple exposures to the virus
PloS one, Vol.10(6), e0130420
2015
Abstract
Characterisation of Hepatitis C virus (HCV)-specific CD8+ T-cell responses in the context of multiple HCV exposures is critical to identify broadly protective immune responses necessary for an effective HCV vaccine against the different HCV genotypes. However, host and viral genetic diversity complicates vaccine development. To compensate for the observed variation in circulating autologous viruses and host molecules that restrict antigen presentation (human leucocyte antigens; HLA), this study used a reverse genomics approach that identified sites of viral adaptation to HLA-restricted T-cell immune pressure to predict genotype-specific HCV CD8+ T-cell targets. Peptides representing these putative HCV CD8+ T-cell targets, and their adapted form, were used in individualised IFN-γ ELISpot assays to screen for HCV-specific T-cell responses in 133 HCV-seropositive subjects with high-risk of multiple HCV exposures. The data obtained from this study i) confirmed that genetic studies of viral evolution is an effective approach to detect novel in vivo HCV T-cell targets, ii) showed that HCV-specific T-cell epitopes can be recognised in their adapted form and would not have been detected using wild-type peptides and iii) showed that HCV-specific T-cell (but not antibody) responses against alternate genotypes in chronic HCV-infected subjects are readily found, implying clearance of previous alternate genotype infection. In summary, HCV adaptation to HLA Class I-restricted T-cell responses plays a central role in anti-HCV immunity and multiple HCV genotype exposure is highly prevalent in at-risk exposure populations, which are important considerations for future vaccine design.
Details
- Title
- Anti-Hepatitis C virus T-Cell immunity in the context of multiple exposures to the virus
- Authors/Creators
- E-C Shin (Author/Creator)K. Pfafferott (Author/Creator) - Murdoch UniversityP. Deshpande (Author/Creator) - The University of Western AustraliaE. McKinnon (Author/Creator) - Murdoch UniversityS. Merani (Author/Creator) - The University of Western AustraliaA. Lucas (Author/Creator) - Murdoch UniversityD. Heckerman (Author/Creator) - Microsoft (Canada)S. Mallal (Author/Creator) - Vanderbilt UniversityM. John (Author/Creator) - Murdoch UniversityS. Gaudieri (Author/Creator) - The University of Western AustraliaM. Lucas (Author/Creator) - The University of Western Australia
- Publication Details
- PloS one, Vol.10(6), e0130420
- Publisher
- Public Library of Science
- Identifiers
- 991005539591907891
- Copyright
- © 2015 Pfafferott et al.
- Murdoch Affiliation
- Institute for Immunology and Infectious Diseases
- Language
- English
- Resource Type
- Journal article
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- Collaboration types
- Industry collaboration
- Domestic collaboration
- International collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.125 Hepatitis
- 1.125.83 HCV
- Web Of Science research areas
- Multidisciplinary Sciences
- ESI research areas
- Clinical Medicine