High spontaneous clearance of symptomatic iatrogenic acute hepatitis C genotype 4 infection.

Acute hepatitis C (AHC) infection resolves spontaneously in 15% to 40% of patients. Factors favoring spontaneous viral clearance remain undefined. In this study, predictors of spontaneous viral clearance in patients with symptomatic AHC were investigated. Epidemiological, clinical, and virologic parameters were also examined. Patients with symptomatic AHC were enrolled and followed up prospectively. The patients were followed up every 2 weeks in the first month and then monthly for the following 5 months, with a follow-up visit 6 months after the last hepatitis C virus (HCV)-RNA negative sample for those who had cleared the virus. Interleukin (IL)-28B.rs12979860 single-nucleotide polymorphism and HCV genotype were tested at baseline. HCV-RNA was tested during each visit. Patients who remained RNA-positive at 24 weeks were treated with pegylated interferon plus ribavirin for 24 weeks. A total of 30 patients, mostly with iatrogenically acquired AHC genotype 4 infections completed 6-months' follow-up, to either spontaneous clearance or start of treatment. The mean age of the patients was 37 ± 13 years. In total, 67% of patients were females, and the mean incubation period was 7.6 ± 3.5 weeks. Viral clearance occurred spontaneously in 19 (63.3%) patients. The average time to clearance was 24.3 ± 9.6 weeks. A total of 11 patients received therapy, and 8 (72.7%) cleared the virus and had a sustained virologic response to the treatment 24 weeks after the therapy. A total of three patients were treatment nonresponders. IL28B.rs12979860 CC genotype, female gender, and viremia level were not associated with self-limiting AHC in this cohort. In conclusion, patients with symptomatic AHC genotype 4 infection caused by an iatrogenic exposure had higher rates of spontaneous resolution than previously reported. Predicting spontaneous viral clearance after iatrogenic AHC exposure was not possible in this population.

Cross reactive cellular immune response to HCV genotype 1 and 4 antigens among genotype 4 exposed subjects.

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)/10(6) 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.

Cellular and humoral immune responses to recombinant Smp17.7 Schistosoma mansoni antigen.

To determine the immunological responses to S. mansoni antigen rSmp17.7, a total of 184 subjects, 174 patients from a schistosomiasis endemic area, and 10 controls were used. Proliferation, cytokine profile in culture supernatants from antigen-stimulated peripheral blood mononuclear cells and specific IgG1, IgG3, IgG4, IgA, IgM & IgE levels were assessed. The highest stimulation index to rSmp17.7 was detected in S. mansoni patients. The evaluation of the cytokine profile [IL-2, IL-4 & IFN-gamma] in response to this antigen showed a significant increase as demonstrated by ELISA. Specifically, IFN-gamma and IL-2 were significantly detected by flow cytometry. IgG1 and IgM were the only Igs which showed a significant increase. These results highlight the importance of rSmp17.7 as a candidate vaccine for schistosomiasis. The results pave the way to understand the mechanism of schistosome-vaccine efficacy.