Cured HCV patients with suboptimal hepatitis B vaccine response exhibit high self-reactive immune signatures

Abstract

Background and Rationale: Chronic HCV infection induces lasting effects on the immune system despite viral clearance. It is unclear whether certain immune alterations are associated with vaccine responses in cured HCV patients. Approach: Thirteen cured HCV patients received the standard 3-dose hepatitis B vaccine and were followed up at the 0, 1st, 6th, and 7th months (M0, M1, M6, and M7) after the first dose of vaccination. Thirty-three-color and 26-color spectral flow cytometry panels were used for high-dimensional immunophenotyping of the T-cell and B-cell subsets, respectively. Results: Compared to the healthy controls (HC), 17 of 43 (39.5%) immune cell subsets showed abnormal frequencies in cured HCV patients. Patients with cured HCV were further divided into high responders (HR, n = 6) and nonresponders (NR1, n = 7) based on the levels of hepatitis B surface antibodies at M1. Alterations in cell populations were more significant in NR1. Moreover, we found that high levels of self-reactive immune signatures, including Tregs, TD/CD8, IgD-only memory B, and autoantibodies, were associated with suboptimal hepatitis B vaccine responses. Conclusions: Our data suggest that cured HCV patients exhibit persistent perturbations in the adaptive immune system, among which highly self-reactive immune signatures may contribute to a suboptimal hepatitis B vaccine response.