BTK inhibitors impair humoral and cellular responses to recombinant zoster vaccine in CLL.
BTK inhibitors impair humoral and cellular responses to recombinant zoster vaccine in CLL.
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DOI：
10.1182/bloodadvances.2021006574
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发表时间：
2022-03-22
期刊：
影响因子：
7.5
通讯作者：
Sun C
中科院分区：
文献类型：
--
作者：
Pleyer C;Laing KJ;Ali MA;McClurkan CL;Soto S;Ahn IE;Nierman P;Maddux E;Lotter J;Superata J;Tian X;Wiestner A;Cohen JI;Koelle DM;Sun C
对RZV的抗体和T细胞免疫反应在TN CLL患者中受损，在接受BTKi治疗的患者中程度更大。虽然抗体和细胞免疫反应通常是一致的，但39%没有抗体反应的患者出现了T细胞反应。接种疫苗可有效预防感染；然而，慢性淋巴细胞白血病(CLL)患者接种疫苗后抗体反应降低。在慢性淋巴细胞白血病中，对新型佐剂疫苗的体液免疫和细胞免疫的联合反应并不是很好的特征。在一项开放标签的单臂临床试验中，我们检测了重组带状疱疹疫苗(RZV)在接受单纯治疗(TN)或接受Bruton酪氨酸激酶抑制剂(BTKi)治疗的CLL患者中的体液和细胞免疫原性。主要终点是对RZV的抗体应答(抗糖蛋白E[≥-GE]增加四倍)。用流式细胞仪检测≥-2效应分子表达上调的细胞反应。与接受BTKI治疗的患者(40.0%；95%CI，26.4-53.6；P=.0002)相比，TN队列中的抗体应答率(76.8%；95%可信区间[CI]，65.7-87.8)显著高于接受BTKI的患者(P=.0002)。TN组的细胞反应率(70.0%；95%CI，57.3-82.7)也明显高于BTKi组(41.3%；95%CI，27.1-55.5；P=0.0072)。在有体液应答的受试者中，69.1%(95%可信区间，56.9~81.3)的受试者体液免疫和细胞免疫应答一致，而在无体液应答的受试者中，细胞免疫应答的符合率为39.0%(95%可信区间，24.1~54.0)(P=0.0033)。抗体滴度和T细胞反应与年龄、B细胞和T细胞绝对计数或血清免疫球蛋白水平无关(均P>；0.05)。RZV在治疗和未治疗的CLL患者中都诱导了体液和细胞免疫反应，尽管BTKi治疗的患者的应答率低于TN患者。这项试验在www.Clinicaltrials.gov上注册为#NCT03702231。
Antibody and T-cell immune responses to RZV are impaired in patients with TN CLL and to a greater extent in patients treated with a BTKi. Although antibody and cellular immune response are often concordant, 39% of patients without antibody response mounted a T-cell response. 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.
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DOI：
10.1093/infdis/jiy095
发表时间：
2018-05-05
期刊：
The Journal of infectious diseases
影响因子：
--
作者：
Cunningham AL;Heineman TC;Lal H;Godeaux O;Chlibek R;Hwang SJ;McElhaney JE;Vesikari T;Andrews C;Choi WS;Esen M;Ikematsu H;Choma MK;Pauksens K;Ravault S;Salaun B;Schwarz TF;Smetana J;Abeele CV;Van den Steen P;Vastiau I;Weckx LY;Levin MJ;ZOE-50/70 Study Group
通讯作者：
ZOE-50/70 Study Group
影响因子：
6.5
作者：
Strati, Paolo;Parikh, Sameer A.;Shanafelt, Tait D.
通讯作者：
Shanafelt, Tait D.
影响因子：
6.4
作者：
Laing, Kerry J.;Russell, Ronnie M.;Koelle, David M.
通讯作者：
Koelle, David M.
影响因子：
3.1
作者：
Steingrimsson, Vilhjalmur;Gislason, Gauti Kjartan;Kristinsson, Sigurdur Y.
通讯作者：
Kristinsson, Sigurdur Y.
影响因子：
20.3
作者：
Hallek, Michael;Cheson, Bruce D.;Kipps, Thomas J.
通讯作者：
Kipps, Thomas J.