Published online Jan 7, 2014. doi: 10.3748/wjg.v20.i1.148
Revised: July 5, 2013
Accepted: July 12, 2013
Published online: January 7, 2014
Processing time: 326 Days and 19 Hours
AIM: To analyze hepatitis C virus (HCV)-specific immune responses in chronically infected patients under triple therapy with interferon-α (IFN-α) plus ribavirin and CIGB-230.
METHODS: CIGB-230 was administered in different schedules with respect to IFN-α plus ribavirin therapy. Paired serum and peripheral blood mononuclear cells (PBMC) samples from baseline and end of treatment were analyzed. The HCV-specific humoral response was tested by enzyme-linked immunosorbent assay, neutralizing antibodies were evaluated by cell culture HCV neutralization assays, PBMC proliferation was assayed by carboxyfluorescein succinimidyl ester staining and IFN-γ secretion was assessed by enzyme-linked immunospot. Data on virological and histological response and their association with immune variables are also provided.
RESULTS: From week 12 to week 48, all groups of patients showed a significant reduction in mean leukocyte counts. Statistically significant reductions in antibody titers were frequent, but only individuals immunized with CIGB-230 as early add-on treatment sustained the core-IgG response, and the neutralizing antibody response was enhanced only in patients receiving CIGB-230. Cell-mediated immune responses also tended to decline, but significant reductions in IFN-γ secretion and total absence of core-specific lymphoproliferation were exclusive of the control group. Only CIGB-230-immunized individuals showed de novo induced lymphoproliferative responses against the structural antigens. Importantly, it was demonstrated that the quality of the CIGB-230-induced immune response depended on the number of doses and timing of administration in relation to the antiviral therapy. Specifically, the administration of 6 doses of CIGB-230 as late add-on to therapy increased the neutralizing antibody activity and the de novo core-specific IFN-γ secretion, both of which were associated with the sustained virological response.
CONCLUSION: CIGB-230, combined with IFN-α-based therapy, modifies the immune response in chronic patients. The study provides evidence for the design of more effective therapeutic vaccine interventions against HCV.
Core tip: We assayed, for the first time, the concomitant administration of CIGB-230, a DNA-based therapeutic vaccine candidate against hepatitis C virus (HCV), and non-peginterferon-α (IFN-α) plus ribavirin therapy to chronic, treatment-naive, HCV genotype 1b infected patients. We showed that CIGB-230 enhanced the neutralizing antibody response and induced de novo proliferative and IFN-γ secretion responses in the context of antiviral therapy. The quality of the induced immune response depended on both the number of doses and the timing of administration in relation to the antiviral therapy. In particular, the increases in neutralizing antibodies and IFN-γ were associated with the sustained virological response.