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

Alex S. Hartlage, Satyapramod Murthy, Arvind Kumar, Sheetal Trivedi, Piyush Dravid, Himanshu Sharma, Christopher M. Walker and Amit Kapoor ()
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Alex S. Hartlage: The Research Institute at Nationwide Children’s Hospital
Satyapramod Murthy: The Research Institute at Nationwide Children’s Hospital
Arvind Kumar: The Research Institute at Nationwide Children’s Hospital
Sheetal Trivedi: The Research Institute at Nationwide Children’s Hospital
Piyush Dravid: The Research Institute at Nationwide Children’s Hospital
Himanshu Sharma: The Research Institute at Nationwide Children’s Hospital
Christopher M. Walker: The Research Institute at Nationwide Children’s Hospital
Amit Kapoor: The Research Institute at Nationwide Children’s Hospital

Nature Communications, 2019, vol. 10, issue 1, 1-11

Abstract: Abstract 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.

Date: 2019
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DOI: 10.1038/s41467-019-09105-0

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