Biomarkers distinguish HBeAg seroconverted from non-converted individuals in chronic hepatitis B patients treated with a therapeutic vaccine

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Abstract

Cytokine assays of host immune responses to vaccination can indicate vaccine efficacy. Here we tested the hypothesis that assays of the cytokine status of infected individuals prior to therapeutic vaccination might provide a guide to vaccine therapeutic efficacy. If so, cytokine analysis might be used to select appropriate patients for therapeutic vaccination. Data were obtained from a panel of 14 cytokine/chemokine assays that were done during a phase III clinical trial of HBsAg-HBIG therapeutic vaccine (YIC) treatment of chronic hepatitis B (CHB) patients. Summarized assay results were compared between patients who responded by HBeAg-seroconversion and non-responders. Though no single cytokine or chemokine showed clear correlation with responsiveness, by bio-mathematical analysis with Boolean modelling, the combined results revealed that plasma IL-10, IL-33 and MIP-1α together correlated best with responsiveness. However, the difference between HBeAg seroconverted and non-converted YIC-treated CHB patients was maximized when results of all 14 cytokine/chemokine assays were included and showed a sensitivity around 0.59, and a specificity of 0.8. It suggested that the combined analysis of these elements may be useful to screen appropriate CHB patients for therapeutic vaccination with YIC.

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