Differential antigenic hierarchy associated with spontaneous recovery from hepatitis C virus infection: implications for vaccine design

J Infect Dis. 2006 Aug 15;194(4):454-63. doi: 10.1086/505714. Epub 2006 Jul 12.


Background: Cellular immune responses play a central role in the control of hepatitis C virus (HCV) infection, and in some individuals the adaptive immune response can spontaneously eradicate HCV infection. The development of vaccine candidates to prevent the spread of this infection remains a top priority; however, understanding the correlates of effective immunological containment is an important prerequisite.

Methods: Using 750 overlapping peptides, we directly characterized ex vivo total and subgenomic HCV-specific CD4(+) and CD8(+) T cell responses in a large cohort of participants with either chronic infection or spontaneously resolved infection.

Results: In chronic infection, the frequency of total CD4(+) T cells specific for HCV averaged 0.06%, compared with 0.38% in resolved infection. Total HCV-specific CD4(+) and CD8(+) T cell responses were strongly correlated in the setting of spontaneous resolution but not in the setting of viral persistence. NS3 protein-specific responses comprised a significantly greater proportion of the total response in resolved infection than in chronic infection, whereas responses to different regions comprised a larger proportion of responses in chronic infection.

Conclusion: Because these data comprehensively define the breadth, specificity, and threshold of the T cell response associated with spontaneous recovery from HCV infection, they have important implications in the development of multigenic vaccine candidates for this common infection.

Publication types

  • Evaluation Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • CD4-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Case-Control Studies
  • Cohort Studies
  • Dendritic Cells / immunology
  • Epitopes / immunology
  • Female
  • Flow Cytometry
  • Hepacivirus / immunology*
  • Hepatitis C / prevention & control*
  • Hepatitis C Antigens / immunology*
  • Humans
  • Male
  • Middle Aged
  • Peptide Fragments / immunology
  • Remission, Spontaneous
  • Viral Hepatitis Vaccines / immunology*
  • Viral Nonstructural Proteins / immunology


  • Epitopes
  • Hepatitis C Antigens
  • NS3 protein, hepatitis C virus
  • Peptide Fragments
  • Viral Hepatitis Vaccines
  • Viral Nonstructural Proteins