Hepatitis C Virus-Multispecific T-Cell Responses without Viremia or Seroconversion among Egyptian Health Care Workers at High Risk of Infection

Hepatitis C virus (HCV)-specific cell-mediated immunity (CMI) has been reported among exposed individuals without viremia or seroconversion. Limited data are available regarding CMI among at-risk, seronegative, aviremic Egyptian health care workers (HCW), where HCV genotype 4 predominates. We investigated CMI responses among HCW at the National Liver Institute, where over 85% of the patients are HCV infected. We quantified HCV-specific CMI in 52 seronegative aviremic Egyptian HCW using a gamma interferon (IFN-gamma) enzyme-linked immunospot assay in response to 7 HCV genotype 4a overlapping 15-mer peptide pools covering most of the viral genome. A positive HCV-specific IFN-gamma response was detected in 29 of 52 HCW (55.8%), where 21 (40.4%) had a positive response for two to seven HCV pools and 8 (15.4%) responded to only one pool. The average numbers of IFN-gamma total spot-forming cells (SFC) per million peripheral blood mononuclear cells (PBMC) (+/- standard error of the mean [SEM]) in the 29 responding and 23 nonresponding HCW were 842 +/- 141 and 64 +/- 15, respectively (P < 0.001). Flow cytometry indicated that both CD4(+) and CD4(-) T cells produced IFN-gamma. In summary, more than half of Egyptian HCW demonstrated strong HCV multispecific CMI without viremia or seroconversion, suggesting possible clearance of low HCV exposure( s). These data suggest that detecting anti-HCV and viremia to determine past exposure to HCV can lead to an underestimation of the true disease exposure and that CMI response may contribute to the low degree of chronic HCV infection in these HCW. These findings could have strong implications for planning vaccine studies among populations with a high HCV exposure rate. Further studies are needed to determine whether these responses are protective.