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HCV p7 as a novel vaccine-target inducing multifunctional CD4(+) and CD8(+) T-cells targeting liver cells expressing the viral antigen
Despite recent treatment advances for chronic hepatitis C virus (HCV) infection, a vaccine is urgently needed for global control of this important liver pathogen. The lack of robust immunocompetent HCV infection models makes it challenging to identify correlates of protection and test vaccine effica...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6773770/ https://www.ncbi.nlm.nih.gov/pubmed/31575882 http://dx.doi.org/10.1038/s41598-019-50365-z |
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author | Filskov, Jonathan Andersen, Peter Agger, Else Marie Bukh, Jens |
author_facet | Filskov, Jonathan Andersen, Peter Agger, Else Marie Bukh, Jens |
author_sort | Filskov, Jonathan |
collection | PubMed |
description | Despite recent treatment advances for chronic hepatitis C virus (HCV) infection, a vaccine is urgently needed for global control of this important liver pathogen. The lack of robust immunocompetent HCV infection models makes it challenging to identify correlates of protection and test vaccine efficacy. However, vigorous CD4(+) and CD8(+) T-cell responses are detected in patients that spontaneously resolve acute infection, whereas dysfunctional T-cell responses are a hallmark of chronic infection. The HCV p7 protein, forming ion-channels essential for viral assembly and release, has not previously been pursued as a vaccine antigen. Herein, we demonstrated that HCV p7 derived from genotype 1a and 1b sequences are highly immunogenic in mice when employed as overlapping peptides formulated as nanoparticles with the cross-priming adjuvant, CAF09. This approach induced multifunctional cytokine producing CD4(+) and CD8(+) T-cells targeting regions of p7 that are subject to immune pressure during HCV infection in chimpanzees and humans. Employing a surrogate in vivo challenge model of liver cells co-expressing HCV-p7 and GFP, we found that vaccinated mice cleared transgene expressing cells. This study affirms the potential of a T-cell inducing nanoparticle vaccine platform to target the liver and introduces HCV p7 as a potential target for HCV vaccine explorations. |
format | Online Article Text |
id | pubmed-6773770 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-67737702019-10-04 HCV p7 as a novel vaccine-target inducing multifunctional CD4(+) and CD8(+) T-cells targeting liver cells expressing the viral antigen Filskov, Jonathan Andersen, Peter Agger, Else Marie Bukh, Jens Sci Rep Article Despite recent treatment advances for chronic hepatitis C virus (HCV) infection, a vaccine is urgently needed for global control of this important liver pathogen. The lack of robust immunocompetent HCV infection models makes it challenging to identify correlates of protection and test vaccine efficacy. However, vigorous CD4(+) and CD8(+) T-cell responses are detected in patients that spontaneously resolve acute infection, whereas dysfunctional T-cell responses are a hallmark of chronic infection. The HCV p7 protein, forming ion-channels essential for viral assembly and release, has not previously been pursued as a vaccine antigen. Herein, we demonstrated that HCV p7 derived from genotype 1a and 1b sequences are highly immunogenic in mice when employed as overlapping peptides formulated as nanoparticles with the cross-priming adjuvant, CAF09. This approach induced multifunctional cytokine producing CD4(+) and CD8(+) T-cells targeting regions of p7 that are subject to immune pressure during HCV infection in chimpanzees and humans. Employing a surrogate in vivo challenge model of liver cells co-expressing HCV-p7 and GFP, we found that vaccinated mice cleared transgene expressing cells. This study affirms the potential of a T-cell inducing nanoparticle vaccine platform to target the liver and introduces HCV p7 as a potential target for HCV vaccine explorations. Nature Publishing Group UK 2019-10-01 /pmc/articles/PMC6773770/ /pubmed/31575882 http://dx.doi.org/10.1038/s41598-019-50365-z Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Filskov, Jonathan Andersen, Peter Agger, Else Marie Bukh, Jens HCV p7 as a novel vaccine-target inducing multifunctional CD4(+) and CD8(+) T-cells targeting liver cells expressing the viral antigen |
title | HCV p7 as a novel vaccine-target inducing multifunctional CD4(+) and CD8(+) T-cells targeting liver cells expressing the viral antigen |
title_full | HCV p7 as a novel vaccine-target inducing multifunctional CD4(+) and CD8(+) T-cells targeting liver cells expressing the viral antigen |
title_fullStr | HCV p7 as a novel vaccine-target inducing multifunctional CD4(+) and CD8(+) T-cells targeting liver cells expressing the viral antigen |
title_full_unstemmed | HCV p7 as a novel vaccine-target inducing multifunctional CD4(+) and CD8(+) T-cells targeting liver cells expressing the viral antigen |
title_short | HCV p7 as a novel vaccine-target inducing multifunctional CD4(+) and CD8(+) T-cells targeting liver cells expressing the viral antigen |
title_sort | hcv p7 as a novel vaccine-target inducing multifunctional cd4(+) and cd8(+) t-cells targeting liver cells expressing the viral antigen |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6773770/ https://www.ncbi.nlm.nih.gov/pubmed/31575882 http://dx.doi.org/10.1038/s41598-019-50365-z |
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