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Vaccination to prevent T cell subversion can protect against persistent hepacivirus infection

Efforts to develop an effective vaccine against the hepatitis C virus (HCV; human hepacivirus) have been stymied by a lack of small animal models. Here, we describe an experimental rat model of chronic HCV-related hepacivirus infection and its response to T cell immunization. Immune-competent rats c...

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Autores principales: Hartlage, Alex S., Murthy, Satyapramod, Kumar, Arvind, Trivedi, Sheetal, Dravid, Piyush, Sharma, Himanshu, Walker, Christopher M., Kapoor, Amit
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6405742/
https://www.ncbi.nlm.nih.gov/pubmed/30846697
http://dx.doi.org/10.1038/s41467-019-09105-0
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author Hartlage, Alex S.
Murthy, Satyapramod
Kumar, Arvind
Trivedi, Sheetal
Dravid, Piyush
Sharma, Himanshu
Walker, Christopher M.
Kapoor, Amit
author_facet Hartlage, Alex S.
Murthy, Satyapramod
Kumar, Arvind
Trivedi, Sheetal
Dravid, Piyush
Sharma, Himanshu
Walker, Christopher M.
Kapoor, Amit
author_sort Hartlage, Alex S.
collection PubMed
description Efforts to develop an effective vaccine against the hepatitis C virus (HCV; human hepacivirus) have been stymied by a lack of small animal models. Here, we describe an experimental rat model of chronic HCV-related hepacivirus infection and its response to T cell immunization. Immune-competent rats challenged with a rodent hepacivirus (RHV) develop chronic viremia characterized by expansion of non-functional CD8(+) T cells. Single-dose vaccination with a recombinant adenovirus vector expressing hepacivirus non-structural proteins induces effective immunity in majority of rats. Resolution of infection coincides with a vigorous recall of intrahepatic cellular responses. Host selection of viral CD8 escape variants can subvert vaccine-conferred immunity. Transient depletion of CD8(+) cells from vaccinated rats prolongs infection, while CD4(+) cell depletion results in chronic viremia. These results provide direct evidence that co-operation between CD4(+) and CD8(+) T cells is important for hepacivirus immunity, and that subversion of responses can be prevented by prophylactic vaccination.
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spelling pubmed-64057422019-03-11 Vaccination to prevent T cell subversion can protect against persistent hepacivirus infection Hartlage, Alex S. Murthy, Satyapramod Kumar, Arvind Trivedi, Sheetal Dravid, Piyush Sharma, Himanshu Walker, Christopher M. Kapoor, Amit Nat Commun Article Efforts to develop an effective vaccine against the hepatitis C virus (HCV; human hepacivirus) have been stymied by a lack of small animal models. Here, we describe an experimental rat model of chronic HCV-related hepacivirus infection and its response to T cell immunization. Immune-competent rats challenged with a rodent hepacivirus (RHV) develop chronic viremia characterized by expansion of non-functional CD8(+) T cells. Single-dose vaccination with a recombinant adenovirus vector expressing hepacivirus non-structural proteins induces effective immunity in majority of rats. Resolution of infection coincides with a vigorous recall of intrahepatic cellular responses. Host selection of viral CD8 escape variants can subvert vaccine-conferred immunity. Transient depletion of CD8(+) cells from vaccinated rats prolongs infection, while CD4(+) cell depletion results in chronic viremia. These results provide direct evidence that co-operation between CD4(+) and CD8(+) T cells is important for hepacivirus immunity, and that subversion of responses can be prevented by prophylactic vaccination. Nature Publishing Group UK 2019-03-07 /pmc/articles/PMC6405742/ /pubmed/30846697 http://dx.doi.org/10.1038/s41467-019-09105-0 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
Hartlage, Alex S.
Murthy, Satyapramod
Kumar, Arvind
Trivedi, Sheetal
Dravid, Piyush
Sharma, Himanshu
Walker, Christopher M.
Kapoor, Amit
Vaccination to prevent T cell subversion can protect against persistent hepacivirus infection
title Vaccination to prevent T cell subversion can protect against persistent hepacivirus infection
title_full Vaccination to prevent T cell subversion can protect against persistent hepacivirus infection
title_fullStr Vaccination to prevent T cell subversion can protect against persistent hepacivirus infection
title_full_unstemmed Vaccination to prevent T cell subversion can protect against persistent hepacivirus infection
title_short Vaccination to prevent T cell subversion can protect against persistent hepacivirus infection
title_sort vaccination to prevent t cell subversion can protect against persistent hepacivirus infection
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6405742/
https://www.ncbi.nlm.nih.gov/pubmed/30846697
http://dx.doi.org/10.1038/s41467-019-09105-0
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