HCV-specific immune responses induced by CIGB-230 in combination with IFN-α plus ribavirin

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-αplus 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-γsecretion 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-γsecretion 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 thequality 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 addon to therapy increased the neutralizing antibody activity and the de novo core-specific IFN-γsecretion,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.