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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...
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/PMC6405742/ https://www.ncbi.nlm.nih.gov/pubmed/30846697 http://dx.doi.org/10.1038/s41467-019-09105-0 |
Sumario: | 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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