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

Abstract

To 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 IFNγ, 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.

Competing Interest Statement

M.S. has received grant support from Astellas and Biotest to the organization Saarland University outside the submitted work, and honoraria for lectures from Biotest and Novartis, and for advisory boards from Moderna, Biotest, MSD and Takeda outside the submitted work. T.S. has received travel grant support from Biotest outside the submitted work. All other authors of this manuscript have no conflicts of interest to disclose.

Funding Statement

Financial support was provided in part by HOMFORexzellent (to D.S.).

Author Declarations

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The study was approved by the ethics committee of the Arztekammer des Saarlandes (reference 27/19), and all individuals gave written informed consent.

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

Data Availability

All data produced in the present study are available upon reasonable request to the authors

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