Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD.
Department of Medicine, University of Washington, Seattle, WA.
Blood Adv. 2022 Mar 22;6(6):1732-1740. doi: 10.1182/bloodadvances.2021006574.
Vaccinations effectively prevent infections; however, patients with chronic lymphocytic leukemia (CLL) have reduced antibody responses following vaccinations. Combined humoral and cellular immune responses to novel adjuvanted vaccines are not well characterized in CLL. In an open-label, single-arm clinical trial, we measured the humoral and cellular immunogenicity of the recombinant zoster vaccine (RZV) in CLL patients who were treatment naïve (TN) or receiving Bruton tyrosine kinase inhibitor (BTKi) therapy. The primary endpoint was antibody response to RZV (≥fourfold increase in anti-glycoprotein E [anti-gE]). Cellular response of gE-specific CD4+ T cells was assessed by flow cytometry for upregulation of ≥2 effector molecules. The antibody response rate was significantly higher in the TN cohort (76.8%; 95% confidence interval [CI], 65.7-87.8) compared with patients receiving a BTKi (40.0%; 95% CI, 26.4-53.6; P = .0002). The cellular response rate was also significantly higher in the TN cohort (70.0%; 95% CI, 57.3-82.7) compared with the BTKi group (41.3%; 95% CI, 27.1-55.5; P = .0072). A concordant positive humoral and cellular immune response was observed in 69.1% (95% CI, 56.9-81.3) of subjects with a humoral response, whereas 39.0% (95% CI, 24.1-54.0) of subjects without a humoral response attained a cellular immune response (P = .0033). Antibody titers and T-cell responses were not correlated with age, absolute B- and T-cell counts, or serum immunoglobulin levels (all P > .05). RZV induced both humoral and cellular immune responses in treated and untreated CLL patients, albeit with lower response rates in patients on BTKi therapy compared with TN patients. This trial was registered at www.clinicaltrials.gov as #NCT03702231.
疫苗可有效预防感染；然而，慢性淋巴细胞白血病 (CLL) 患者接种疫苗后的抗体反应会下降。新型佐剂疫苗的体液和细胞免疫反应在 CLL 中尚未得到充分描述。在一项开放标签、单臂临床试验中，我们测量了初治（TN）或接受布鲁顿酪氨酸激酶抑制剂（BTKi）治疗的 CLL 患者重组带状疱疹疫苗（RZV）的体液和细胞免疫原性。主要终点是对 RZV 的抗体反应（抗糖蛋白 E [抗-gE] 增加四倍以上）。通过流式细胞术评估 gE 特异性 CD4+T 细胞的细胞反应，以评估上调≥2 种效应分子的情况。与接受 BTKi 治疗的患者相比，TN 队列的抗体反应率显著更高（76.8%；95%置信区间 [CI]，65.7-87.8）（P =.0002）。与 BTKi 组相比，TN 队列的细胞反应率也显著更高（70.0%；95%CI，57.3-82.7）（P =.0072）。在有体液反应的受试者中，69.1%（95%CI，56.9-81.3）观察到体液和细胞免疫反应呈阳性一致，而在没有体液反应的受试者中，39.0%（95%CI，24.1-54.0）获得细胞免疫反应（P =.0033）。抗体滴度和 T 细胞反应与年龄、绝对 B 细胞和 T 细胞计数或血清免疫球蛋白水平均无相关性（均 P >.05）。RZV 在接受治疗和未接受治疗的 CLL 患者中均诱导了体液和细胞免疫反应，尽管与 TN 患者相比，接受 BTKi 治疗的患者的反应率较低。该试验在 www.clinicaltrials.gov 上注册为 #NCT03702231。
