DataSheet_1_Boosting the VZV-Specific Memory B and T Cell Response to Prevent Herpes Zoster After Kidney Transplantation.pdf

BackgroundSolid organ transplant recipients are at high risk to develop (complicated) herpes zoster (HZ). Booster vaccination could prevent HZ. However, end-stage renal disease (ESRD) patients show poor immunological responses to vaccinations. We studied the effect of a live attenuated VZV booster vaccine on VZV-specific B and T cell memory responses in ESRD patients and healthy controls. NL28557.000.09, www.toetsingonline.nl
MethodsVZV-seropositive patients, aged ≥50 years, awaiting kidney transplantation, were vaccinated with Zostavax®. Gender and age-matched VZV-seropositive potential living kidney donors were included as controls. VZV-specific IgG titers were measured before, at 1, 3 and 12 months post-vaccination. VZV-specific B and T cell responses before, at 3 months and 1 year after vaccination were analysed by flow-cytometry and Elispot, respectively. Occurrence of HZ was assessed at 5 years post-vaccination.
Results26 patients and 27 donors were included. Median VZV-specific IgG titers were significantly higher at all time-points post-vaccination in patients (mo 1: 3104 IU/ml [1967-3825], p<0.0001; mo 3: 2659 [1615-3156], p=0.0002; mo 12: 1988 [1104-2989], p=0.01 vs. pre: 1397 [613-2248]) and in donors (mo 1: 2981 [2126-3827], p<0.0001; mo 3: 2442 [2014-3311], p<0.0001; mo 12: 1788 [1368-2460], p=0.0005 vs. pre: 1034 [901-1744]. The patients’ IgG titers were comparable to the donors’ at all time-points. The ratio VZV-specific B cells of total IgG producing memory B cells had increased 3 months post-vaccination in patients (0.85 [0.65-1.34] vs. pre: 0.56 [0.35-0.81], p=0.003) and donors (0.85 [0.63-1.06] vs. pre: 0.53 [0.36-0.79], p<0.0001) and remained stable thereafter in donors. One year post-vaccination, the percentage of CD4+ central memory cells had increased in both patients (0.29 [0.08-0.38] vs. 0.12 [0.05-0.29], p=0.005) and donors (0.12 [0.03-0.37] vs. 0.09 [0.01-0.20], p=0.002) and CD4+ effector memory cells had increased in donors (0.07 [0.02-0.14] vs. 0.04 [0.01-0.12], p=0.007). Only 1 patient experienced HZ, which was non-complicated.
ConclusionVZV booster vaccination increases VZV-specific IgG titers and percentage VZV-specific memory T-cells for at least 1 year both in ESRD patients and healthy controls. VZV-specific memory B cells significantly increased in patients up to 3 months after vaccination. Prophylactic VZV booster vaccination prior to transplantation could reduce HZ incidence and severity after transplantation.

背景：实体器官移植受者罹患（复杂性）带状疱疹（herpes zoster, HZ）的风险极高。加强疫苗接种可预防带状疱疹的发生。然而，终末期肾病（end-stage renal disease, ESRD）患者对疫苗接种的免疫应答效果较差。本研究探讨了减毒活水痘带状疱疹病毒（varicella-zoster virus, VZV）加强疫苗对终末期肾病患者及健康对照者体内VZV特异性B细胞和T细胞记忆应答的影响。NL28557.000.09，www.toetsingonline.nl

方法：纳入年龄≥50岁、血清VZV抗体阳性且等待肾移植的患者，给予佐斯达克斯®（Zostavax®）疫苗接种。以性别和年龄相匹配的、血清VZV抗体阳性的潜在活体肾捐献者作为对照。分别于疫苗接种前、接种后1、3及12个月检测VZV特异性IgG滴度。于疫苗接种前、接种后3个月及1年，分别通过流式细胞术（flow-cytometry）与酶联免疫斑点试验（Elispot）分析VZV特异性B细胞与T细胞应答。并于疫苗接种后5年评估带状疱疹的发生情况。

结果：本研究共纳入26例患者与27名捐献者。与接种前（患者组：1397 IU/ml [613-2248]；捐献者组：1034 IU/ml [901-1744]）相比，患者组与捐献者组在接种后各时间点的VZV特异性IgG滴度均显著升高：患者组（1个月：3104 IU/ml [1967-3825]，p<0.0001；3个月：2659 IU/ml [1615-3156]，p=0.0002；12个月：1988 IU/ml [1104-2989]，p=0.01）；捐献者组（1个月：2981 IU/ml [2126-3827]，p<0.0001；3个月：2442 IU/ml [2014-3311]，p<0.0001；12个月：1788 IU/ml [1368-2460]，p=0.0005）。两组在各时间点的IgG滴度均无显著差异。患者组与捐献者组中，接种后3个月时，总IgG产生性记忆B细胞中VZV特异性B细胞的比例均显著升高（患者组：0.85 [0.65-1.34] vs 接种前0.56 [0.35-0.81]，p=0.003；捐献者组：0.85 [0.63-1.06] vs 接种前0.53 [0.36-0.79]，p<0.0001），且捐献者组该比例在后续时间点保持稳定。接种后1年，两组的CD4+中枢记忆T细胞比例均显著升高（患者组：0.29 [0.08-0.38] vs 接种前0.12 [0.05-0.29]，p=0.005；捐献者组：0.12 [0.03-0.37] vs 接种前0.09 [0.01-0.20]，p=0.002）；捐献者组的CD4+效应记忆T细胞比例亦显著升高（0.07 [0.02-0.14] vs 接种前0.04 [0.01-0.12]，p=0.007）。本研究中仅1例患者出现非复杂性带状疱疹。

结论：无论终末期肾病患者还是健康对照者，VZV加强疫苗接种均可至少1年提升VZV特异性IgG滴度与VZV特异性记忆T细胞比例。患者体内的VZV特异性记忆B细胞比例在接种后3个月内显著升高。肾移植前预防性给予VZV加强疫苗接种，可降低移植后带状疱疹的发生率与严重程度。