Successful vaccination induces multifunctional memory T-cell precursors associated with early control of hepatitis C virus

Gastroenterology. 2012 Oct;143(4):1048-60.e4. doi: 10.1053/j.gastro.2012.06.005. Epub 2012 Jun 13.


Background & aims: T cells are an important component for development of a vaccine against hepatitis C virus (HCV), but little is known about the features of successful vaccine-induced T cells.

Methods: We compared the phenotype, function, and kinetics of vaccine-induced and infection-induced T cells in chimpanzees with HCV infection using multicolor flow cytometry and real-time polymerase chain reaction.

Results: In chimpanzees successfully vaccinated with recombinant adenovirus and DNA against HCV NS3-5, HCV-specific T cells appeared earlier, maintained better functionality, and persisted at higher frequencies for a longer time after HCV challenge, than those of mock-vaccinated chimpanzees. Vaccine-induced T cells displayed higher levels of CD127, a marker of memory precursors, and lower levels of programmed death-1 (PD-1) than infection-induced T cells. Vaccine-induced, but not infection-induced, T cells were multifunctional; their ability to secrete interferon gamma and tumor necrosis factor α correlated with early expression of CD127 but not PD-1. Based on a comparison of vaccine-induced and infection-induced T cells from the same chimpanzee, the CD127(+) memory precursor phenotype was induced by the vaccine itself rather than by low viremia. In contrast, induction of PD-1 correlated with viremia, and levels of intrahepatic PD-1, PD-L1, and 2,5-OAS-1 messenger RNAs correlated with peak titers of HCV.

Conclusions: Compared with infection, vaccination-induced HCV-specific CD127(+) T cells with high functionality that persisted at higher levels for a longer time. Control of viremia prevented up-regulation of PD-1 on T cells and induction of PD-1, PD-L1, and 2,5-OAS-1 in the liver. Early development of a memory T-cell phenotype and, via control of viremia, attenuation of the inhibitory PD1-PD-L1 pathway might be necessary components of successful vaccine-induced protection against HCV.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2',5'-Oligoadenylate Synthetase / genetics
  • Analysis of Variance
  • Animals
  • B7-H1 Antigen / genetics
  • CD8-Positive T-Lymphocytes / drug effects
  • CD8-Positive T-Lymphocytes / metabolism
  • DNA, Viral / immunology
  • Hepacivirus / immunology*
  • Hepatitis C / immunology*
  • Hepatitis C / metabolism
  • Immunologic Memory
  • Interferon-gamma / metabolism
  • Interleukin-7 Receptor alpha Subunit / metabolism
  • Liver / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Pan troglodytes
  • Phenotype
  • Precursor Cells, T-Lymphoid / drug effects*
  • Precursor Cells, T-Lymphoid / metabolism*
  • Programmed Cell Death 1 Receptor / genetics
  • Programmed Cell Death 1 Receptor / metabolism
  • RNA, Messenger / metabolism
  • Statistics, Nonparametric
  • Tumor Necrosis Factor-alpha / metabolism
  • Vaccination*
  • Viral Hepatitis Vaccines / immunology*
  • Viral Hepatitis Vaccines / pharmacology
  • Viral Load


  • B7-H1 Antigen
  • DNA, Viral
  • Interleukin-7 Receptor alpha Subunit
  • Programmed Cell Death 1 Receptor
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • Viral Hepatitis Vaccines
  • Interferon-gamma
  • 2',5'-Oligoadenylate Synthetase