Hepatitis C virus-specific T cell responses against conserved regions in recovered patients.

For the design of peptide-based vaccines against the hepatitis C virus it is essential to acquire more information on frequently recognized epitopes in patients with successful immune control of HCV in the context of different HLA types. A matrix approach using 393 15mer peptides from conserved HCV regions overlapping by 13 amino acids was applied in 52 HCV-recovered individuals. Candidate peptides were further tested in two independent laboratories. 38 peptides induced IFN-gamma responses in ELISPOT assays including 15 previously unknown epitopes. There was no particular immune dominance as only five peptides were recognized by more than three individuals. Seven out of 14 peptides tested in more detail could be confirmed to be immunogenic using ELISPOT and cytotoxicity assays. While only 33% of HCV-recovered individuals recognized recombinant HCV proteins, 81% of individuals tested positive in the matrix approach (p<0.001). The strength, frequency and breadth of HCV-specific T cell responses were similar in spontaneously recovered patients than in interferon-recovered patients. In conclusion (i) we identified novel HCV epitopes in conserved regions, (ii) confirmed the inter-individual diversity of HCV-specific T cell responses and (iii) found no significant differences in HCV-specific T cell responses between spontaneously recovered and IFN-recovered patients.

[Injuries from needles contaminated with hepatitis C virus: how high is the risk of seroconversion for medical personnel really?]. / Verletzungen mit Hepatitis-C-Virus-kontaminierten Nadeln : Wie hoch ist das Risiko einer Serokonversion bei medizinischem Personal wirklich?

The risk of infection after injury with a needle contaminated with hepatitis C virus (HCV) is thought to be about 3%, but this assumption is mainly based on studies published in the 1990's, which were limited by small sample sizes and insensitive HCV-RNA assays. We therefore investigated needle injuries at the Hannover Medical School over a period of 6 years and performed a systematic review of the literature identifying 22 studies with a total of 6,956 injuries with HCV contaminated needles. Between 2000 and 2005, 1,431 occupational injuries were reported at our institution and two-thirds were needle injuries. Index patients were known to be HCV infected in 166 cases but there were no cases of HCV seroconversion during follow-up. Analysis of published data showed seroconversion rates of 0-10.3% with a mean of 0.75% (52/6,956). The risk of acute HCV infection was lower in Europe with 0.42% compared to Eastern Asia with 1.5% of cases where an HCV viremia was reported during follow-up. In summary, the risk of acquiring an HCV infection after a needlestick injury is lower than frequently reported. Worldwide differences in HCV seroconversion rates suggest that genetic factors might provide some level of natural resistance against HCV. Future studies should address not only the frequency of acute hepatitis but also factors associated with a higher risk of becoming HCV infected.

Induction of hepatitis C virus (HCV)-specific T cells by needle stick injury in the absence of HCV-viraemia.

BACKGROUND: The risk of hepatitis C virus (HCV) infection after occupational exposure is low with seroconversion rates between 0 and 5%. However, factors associated with natural resistance against HCV after needle stick injury are poorly defined. HCV-specific T-cell responses have been described in cross-sectional studies of exposed HCV-seronegative individuals. MATERIALS AND METHODS: In this study, we prospectively followed 10 healthcare professionals who experienced an injury with an HCV-contaminated needle. Blood samples were taken on the day or the day after the event and at different time points during follow-up for up to 32 months. HCV-specific T-cell responses were investigated directly ex vivo and in T-cell lines. RESULTS: None of the individuals became positive for HCV-RNA in serum tested with the highly sensitive transcription-mediated amplification (TMA)-assay or in peripheral blood mononuclear cells (PBMC). All of them remained anti-HCV negative throughout follow-up. At the time of injury, HCV-specific CD4+ T-cell responses were already detectable in two individuals and became detectable thereafter in three additional persons. Transient HCV-specific CD8+ T-cell responses developed in two HLA-A2 positive patients, which became negative until the most recent follow-up after 5 and 17 months, respectively. CONCLUSION: We demonstrate the development of HCV-specific T cells in HCV-exposed individuals after needle stick injury indicating subinfectious exposure to HCV. T-cell immunity against HCV may contribute to the low prevalence of HCV in medical healthcare professionals in Western countries.