2. Academic Validation
  3. Vaccination to prevent T cell subversion can protect against persistent hepacivirus infection

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

  • Nat Commun. 2019 Mar 7;10(1):1113. doi: 10.1038/s41467-019-09105-0.
Alex S Hartlage 1 2,  Satyapramod Murthy 1,  Arvind Kumar 1,  Sheetal Trivedi 1,  Piyush Dravid 1,  Himanshu Sharma 1,  Christopher M Walker 1 3,  Amit Kapoor 4 5
Affiliations

Affiliations

  • 1 Center for Vaccines and Immunity, The Research Institute at Nationwide Children's Hospital, Columbus, OH, 43205, USA.
  • 2 Medical Scientist Training Program, College of Medicine and Public Health, The Ohio State University, Columbus, OH, 43210, USA.
  • 3 Department of Pediatrics, College of Medicine and Public Health, The Ohio State University, Columbus, OH, 43210, USA.
  • 4 Center for Vaccines and Immunity, The Research Institute at Nationwide Children's Hospital, Columbus, OH, 43205, USA. amit.kapoor@nationwidechildrens.org.
  • 5 Department of Pediatrics, College of Medicine and Public Health, The Ohio State University, Columbus, OH, 43210, USA. amit.kapoor@nationwidechildrens.org.
PMID: 30846697 DOI: 10.1038/s41467-019-09105-0
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.

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