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Galal I.F.,Egyptian Company for Blood Transfusion Services Egyblood VACSERA | Zakaria Z.,Egyptian Company for Blood Transfusion Services Egyblood VACSERA | Allam W.R.,Egyptian Company for Blood Transfusion Services Egyblood VACSERA | Mahmoud M.A.,Menoufia University | And 6 more authors.

Background: Hepatitis C Virus (HCV) infection is a global health burden particularly in Egypt, where HCV genotype 4a (GT-4a) predominates. The prevention and control of HCV infection will remain a challenge until the development of an effective vaccine that protects against different genotypes. Several HCV GT-1-based vaccines are in different stages of clinical trials, but antigenic differences could make protection against other genotypes problematic. In this regard, data comparing the cell-mediated immune (CMI) response to different HCV genotypes are limited. We aimed to ex vivo investigate whether GT-1-based vaccine may protect against HCV GT-4 infections. This was carried out on samples collected from genotype 4 infected/exposed subjects. Methods/Principal Findings: The CMI responses of 35 subjects; infected with HCV GT-4/or who had spontaneously-resolved the infection and 10 healthy control subjects; to two sets of seven HCV overlapping 15-mer peptide pools derived from both genotypes; and covering most of the viral proteins; were evaluated. This was carried out using an interferon gamma (IFNγ) enzyme-linked immunospot (ELISpot) assay. Peripheral blood mononuclear cells (PBMC) from 17 subjects (48%) responded to at least one peptide pool derived from GT-1b/GT-4a with 13 subjects responding to peptide pools from both genotypes. A strong correlation was found in the responses to both genotypes (r = 0.82, p<0.001; 95% confidence interval = 0.562-0.933). The average IFNγ total spot forming cells (SFC)/106 PBMC (±SE) from the responding subjects for GT-1b and GT-4a was 216±56 and 199±55, respectively (p = 0.833). Also, there were no significant differences between those who cleared their HCV infection or who remained HCV-RNA positive (p = 0.8). Conclusion/Significance: Our data suggest that an effective GT-1b vaccine could protect from GT-4a infection. These data could help in HCV rationale vaccine design and efficacy studies and further our understanding of HCV cross protection against different genotypes. © 2014 Galal et al. Source

Abdelwahab S.F.,Minia University | Abdelwahab S.F.,Egyptian Company for Blood Transfusion Services Egyblood VACSERA | Zakaria Z.,Egyptian Company for Blood Transfusion Services Egyblood VACSERA | Sobhy M.,Egyptian Company for Blood Transfusion Services Egyblood VACSERA | And 11 more authors.
Clinical and Vaccine Immunology

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-γ) 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-γ 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-γ 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-γ. 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. Copyright © 2012, American Society for Microbiology. Source

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