带状疱疹灭活疫苗 HZ/su 可诱导透析患者产生水痘-带状疱疹病毒特异性细胞和体液免疫应答。

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

机构信息

Department of Transplant and Infection Immunology, Saarland University, Homburg, Germany.

Labor Enders und Partner, Stuttgart, Germany.

出版信息

EBioMedicine. 2024 Oct;108:105335. doi: 10.1016/j.ebiom.2024.105335. Epub 2024 Sep 11.

DOI:10.1016/j.ebiom.2024.105335

PMID:39265505

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11416227/

Abstract

BACKGROUND

To evaluate the immunogenicity of the inactivated herpes-zoster vaccine HZ/su in patients at increased risk for VZV-reactivation, we analysed the quantity and quality of the vaccine-induced cellular and humoral immunity in patients on dialysis with uremic immunodeficiency.

METHODS

In this observational study, 29 patients and 39 immunocompetent controls underwent standard dual-dose vaccination. Blood samples were analysed 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 analysed using ELISA.

FINDINGS

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).

INTERPRETATION

VZV-gE vaccination induced specific antibodies and CD4 T-cells in both patients and controls, whereas CD8 T-cell-induction was poor. Quantitative and qualitative differences in immunity may indicate reduced duration of protection which may necessitate booster vaccinations in patients on dialysis.

FUNDING

HOMFORexzellent (to D.S.).

摘要

背景

为了评估带状疱疹灭活疫苗 HZ/su 在 VZV 再激活风险增加的患者中的免疫原性，我们分析了血液透析伴尿毒症免疫缺陷患者中疫苗诱导的细胞和体液免疫的数量和质量。

方法

在这项观察性研究中，29 名患者和 39 名免疫功能正常的对照者接受了标准的双剂量疫苗接种。在每次接种前和接种后两周以及一年后采集血样进行分析。使用流式细胞术根据细胞因子和 CTLA-4 表达的诱导来鉴定 VZV-gE-肽刺激后的特异性 T 细胞。使用 ELISA 分析抗体。

结果

两组的 VZV-gE 特异性 CD4 T 细胞水平均随时间增加（p<0.0001），尽管第二次接种后达到的中位数水平在患者中较低（0.17%（IQR 0.21%））比对照组（0.24%（IQR 0.3%），p=0.042）。VZV-gE 特异性 CD8 T 细胞的诱导较差。VZV-gE 特异性 CD4 T 细胞上 CTLA-4 的表达在第二次接种后最强，两组之间无差异（p=0.45）。第一次接种后，患者中同时表达 IFNγ、IL-2 和 TNF 的多功能细胞更高（p=0.028）。VZV 特异性 IgG 水平在第二次接种后达到最大值，患者中的水平明显低于对照组（10796（IQR 12482）IU/l）比对照组（16899（IQR 14019）IU/l，p=0.009）。尽管一年后 CD4 T 细胞水平相似（p=0.415），但患者的抗体水平仍明显较低（p=0.0008）。