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

Author

Listed:
  • Alex S. Hartlage

    (The Research Institute at Nationwide Children’s Hospital
    The Ohio State University)

  • 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
    The Ohio State University)

  • Amit Kapoor

    (The Research Institute at Nationwide Children’s Hospital
    The Ohio State University)

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.

Suggested Citation

  • Alex S. Hartlage & Satyapramod Murthy & Arvind Kumar & Sheetal Trivedi & Piyush Dravid & Himanshu Sharma & Christopher M. Walker & Amit Kapoor, 2019. "Vaccination to prevent T cell subversion can protect against persistent hepacivirus infection," Nature Communications, Nature, vol. 10(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-09105-0
    DOI: 10.1038/s41467-019-09105-0
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