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
  • 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. [email protected].
  • 5. Department of Pediatrics, College of Medicine and Public Health, The Ohio State University, Columbus, OH, 43210, USA. [email protected].
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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