Objectives Patients with immune-mediated rheumatic diseases (IMRDs) face an elevated risk of varicella-zoster virus infection (VZV), and herpes zoster (HZ). Treatment with immunosuppressors further increases the risk. A new recently approved adjuvant recombinant inactive vaccine, offers safe protection against HZ. However, limited data exist on the efficacy of this new vaccine in patients with IMRDs treated with JAK inhibitors. We aimed to characterize B cell and T cell immune responses elicited by the HZ recombinant subunit vaccine in patients with IMRDs under treatment with JAK inhibitors, and to identify factors that might be associated with reduced immunogenicity, and therefore reduced protection. Methods We investigated humoral, and cellular CD4 and CD8 immune responses following a two-dose regimen of the recombinant inactive vaccine in 43 patients with rheumatic diseases treated with different JAK inhibitors. The responses were compared with age, gender and disease-matched healthy controls. Results Patients with IMRDs treated with JAK inhibitors showed reduced seroconversion rate (63% vs 100% and lower VZV IgG titers (1222 ± 411 vs 3048 ± 556, p< 0.0001) as compared with healthy controls. Functional T CD4 (IL-2 plus IFN-γ secretion) and T CD8 (Granzyme A and/or Granzyme B secretion) immune responses were also significantly diminished in IMRDs patients. Negative correlation was found between VZV antibody titers and age, specific treatments (baricitinib, tofacitinib, upadacitinib), cumulative methotrexate and glucocorticoid doses, history of multiple DMARDs, and treatment duration with JAK inhibitors. Functional T-CD4 responses but not functional T-CD8 responses also showed similar negative correlations. Positive associations were observed between functional T-CD4 and T-CD8 responses. Conclusions Our study provides valuable insights into the immune responses elicited by the recombinant inactive vaccine in patients with IMRDs treated with JAK inhibitors. In these patients we have observed a broad impact on the adaptive humoral and cellular immune responses, suggesting a potential reduction in protection against herpes zoster infection and VHZ reactivation.

中文翻译：

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JAK 抑制剂治疗免疫介导的风湿病患者对带状疱疹重组亚单位疫苗的免疫原性


目的 免疫介导的风湿病 （IMRDs） 患者患水痘-带状疱疹病毒感染 （VZV） 和带状疱疹 （HZ） 的风险升高。免疫抑制剂治疗会进一步增加风险。一种最近批准的新型佐剂重组灭活疫苗，可针对带状疱疹提供安全保护。然而，关于这种新疫苗对接受 JAK 抑制剂治疗的 IMRD 患者的疗效的数据有限。我们旨在表征 HZ 重组亚单位疫苗在接受 JAK 抑制剂治疗的 IMRD 患者中引发的 B 细胞和 T 细胞免疫反应，并确定可能与免疫原性降低相关的因素，从而降低保护作用。方法 我们研究了 43 例接受不同 JAK 抑制剂治疗的风湿性疾病患者在两剂重组灭活疫苗方案后的体液和细胞 CD4 和 CD8 免疫反应。将反应与年龄、性别和疾病匹配的健康对照进行比较。结果 与健康对照相比，接受 JAK 抑制剂治疗的 IMRD 患者血清转化率降低 （63% vs 100% 和 VZV IgG 滴度降低 （1222 ± 411 vs 3048 ± 556，p< 0.0001）。IMRDs 患者的功能性 T CD4 （IL-2 加 IFN-γ 分泌） 和 T CD8 （颗粒酶 A 和/或颗粒酶 B 分泌） 免疫反应也显着降低。发现 VZV 抗体滴度与年龄、特异性治疗 （baricitinib、tofacitinib、upadacitinib）、累积甲氨蝶呤和糖皮质激素剂量、多种 DMARD 病史以及 JAK 抑制剂治疗持续时间呈负相关。功能性 T-CD4 反应而非功能性 T-CD8 反应也显示出类似的负相关。 在功能性 T-CD4 和 T-CD8 反应之间观察到正相关。结论 我们的研究为重组非活性疫苗在接受 JAK 抑制剂治疗的 IMRD 患者中引发的免疫反应提供了有价值的见解。在这些患者中，我们观察到对适应性体液和细胞免疫反应的广泛影响，表明对带状疱疹感染和 VHZ 再激活的保护可能会降低。