The inactivated herpes zoster vaccine HZ/su induces a varicella zoster virus specific cellular and humoral immune response in dialysis patients

Abstract

AbstractTo evaluate the immunogenicity of the inactivated herpes zoster vaccine HZ/su in patients at increased risk for VZV-reactivation, we analyzed the quantity and quality of the vaccine-induced cellular and humoral immunity in dialysis patients with uremic immunodeficiency.In this observational study, 29 patients and 39 immunocompetent controls underwent standard dual-dose vaccination. Blood samples were analyzed before and two weeks after each vaccination, and after one year. Specific T-cells were characterized after stimulation with VZV-gE peptides based on induction of cytokines and CTLA-4-expression using flow-cytometry. Antibodies were analyzed using ELISA.Both groups showed an increase in VZV-gE specific CD4 T-cell levels over time (p<0.0001), although median levels reached after second vaccination were lower in patients (0.17% (IQR 0.21%)) than in controls (0.24% (IQR 0.3%), p=0.042). VZV-gE specific CD8 T-cells were only poorly induced. CTLA-4 expression on VZV-gE specific CD4 T-cells was strongest after second dose with no differences between the groups (p=0.45). Multifunctional cells co-expressing IFNɣ, IL-2, and TNF were higher in patients after first vaccination (p=0.028). Median VZV-specific IgG-levels reached a maximum after second vaccination with significantly lower levels in patients (10796 (IQR 12482) IU/l) than in controls (16899 (IQR 14019) IU/l, p=0.009). Despite similar CD4 T-cell levels after one year (p=0.415), antibody levels remained significantly lower in patients (p=0.0008).The VZV-gE vaccine induced specific antibodies and CD4 T-cells in both patients and controls, whereas CD8 T-cells were only poorly induced. Quantitative and qualitative differences in immunity in patients may indicate reduced duration of protection which may necessitate booster vaccinations.Graphical abstractLay SummaryLittle is known about the immunogenicity of the inactivated HZ/su in dialysis patients who are at increased risk for VZV reactivation. We therefore analyzed and characterized the cellular and humoral immune response induced by HZ/su in dialysis patients compared to healthy individuals. HZ/su induces VZV-specific CD4 T-cells and antibodies in both controls and dialysis patients, whereas VZV-specific CD8 T-cells were only poorly induced. VZV-specific CD4 T-cells were multifunctional and showed a dynamic increase with a maximum after the second vaccination. However, median T-cell levels were lower in patients. Also VZV-specific IgG antibodies showed a dynamic increase in both groups, although after second vaccination and one year after vaccination antibody levels of patients were lower compared to controls. Future studies should address whether differences in quantity and quality of vaccine-induced VZV-specific T-cells and lower antibody levels in patients may indicate a reduced protective effect, which may necessitate booster vaccinations.