扎努鲁替尼治疗的慢性淋巴细胞白血病患者在5次SARS-CoV-2疫苗接种中的局部和全身免疫

IF 1.3 Q4 HEMATOLOGY
Maria Andersson, Jinghua Wu, David Wullimann, Yu Gao, Mikael Aberg, Sandra Muschiol, Katie Healy, Sabrina Naud, Gordana Bogdanovic, Marzia Palma, Hakan Mellstedt, Puran Chen, Hans-Gustaf Ljunggren, Lotta Hansson, Margaret Sallberg Chen, Marcus Buggert, Hanna M Ingelman-Sundberg, Anders Osterborg
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引用次数: 0

摘要

背景:慢性淋巴细胞白血病(CLL)患者易感染2019冠状病毒病(COVID-19),并且对严重急性呼吸综合征冠状病毒2 (SARS-CoV-2)疫苗接种反应较差,特别是如果使用第一代布鲁顿酪氨酸激酶抑制剂(BTKi)依鲁替尼治疗。我们的目的是评估第三代BTKi zanubrutinib对SARS-CoV-2疫苗接种的全身和粘膜反应的影响。方法:纳入9例正在接受扎鲁替尼治疗的CLL患者,并在SARS-CoV-2疫苗接种期间、疫苗剂量3和5之前以及疫苗剂量3、4和5后2 - 3周捐献血液和唾液。伊鲁替尼治疗的对照患者(n = 7)和年龄匹配的健康对照患者(n = 7)在疫苗剂量5后2 - 3周献血。我们量化了血清和唾液中sars - cov -2特异性IgG和IgA抗体(Abs)的反应性和中和能力,以及被病毒肽激活的T细胞的反应性。结果:与健康对照相比,扎鲁替尼和依鲁替尼治疗的患者在第5剂量后的总尖峰特异性Ab水平均显著降低了1000倍(P < 0.01)。扎鲁替尼治疗患者血清中峰值igg水平与中和能力相关(r = 0.68;P < 0.0001),因此具有功能性。zanubrutinib治疗的患者即使在接种了5剂疫苗后,实际上也没有粘膜免疫(血清和唾液中的特异性IgA),而健康对照组的免疫水平(在接种了5剂疫苗后的血清中检测)显著升高(P < 0.05)。相比之下,扎鲁替尼和依鲁替尼治疗的患者对SARS-CoV-2肽的t细胞反应性与健康对照供体相同高。结论:在扎努鲁替尼治疗的CLL患者的小队列中,我们得出结论,多达五剂的SARS-CoV-2疫苗未诱导可检测到的IgA粘膜免疫,这可能会损害针对感染的初级屏障防御。全身IgG反应也受损,而t细胞反应正常。需要进一步和更大规模的研究来评估这些发现对疾病保护的影响。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Local and Systemic Immunity During Five Vaccinations Against SARS-CoV-2 in Zanubrutinib-Treated Patients With Chronic Lymphocytic Leukemia.

Local and Systemic Immunity During Five Vaccinations Against SARS-CoV-2 in Zanubrutinib-Treated Patients With Chronic Lymphocytic Leukemia.

Local and Systemic Immunity During Five Vaccinations Against SARS-CoV-2 in Zanubrutinib-Treated Patients With Chronic Lymphocytic Leukemia.

Background: Patients with chronic lymphocytic leukemia (CLL) are vulnerable to coronavirus disease 2019 (COVID-19) and are at risk of inferior response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination, especially if treated with the first-generation Bruton's tyrosine kinase inhibitor (BTKi) ibrutinib. We aimed to evaluate the impact of the third-generation BTKi, zanubrutinib, on systemic and mucosal response to SARS-CoV-2 vaccination.

Methods: Nine patients with CLL with ongoing zanubrutinib therapy were included and donated blood and saliva during SARS-CoV-2 vaccination, before vaccine doses 3 and 5 and 2 - 3 weeks after doses 3, 4, and 5. Ibrutinib-treated control patients (n = 7) and healthy aged-matched controls (n = 7) gave blood 2 - 3 weeks after vaccine dose 5. We quantified reactivity and neutralization capacity of SARS-CoV-2-specific IgG and IgA antibodies (Abs) in both serum and saliva, and reactivity of T cells activated with viral peptides.

Results: Both zanubrutinib- and ibrutinib-treated patients had significantly, up to 1,000-fold, lower total spike-specific Ab levels after dose 5 compared to healthy controls (P < 0.01). Spike-IgG levels in serum from zanubrutinib-treated patients correlated well to neutralization capacity (r = 0.68; P < 0.0001) and were thus functional. Mucosal immunity (specific IgA in serum and saliva) was practically absent in zanubrutinib-treated patients even after five vaccine doses, whereas healthy controls had significantly higher levels (tested in serum after vaccine dose 5) (P < 0.05). In contrast, T-cell reactivity against SARS-CoV-2 peptides was equally high in zanubrutinib- and ibrutinib-treated patients as in healthy control donors.

Conclusions: In our small cohort of zanubrutinib-treated CLL patients, we conclude that up to five doses of SARS-CoV-2 vaccination induced no detectable IgA mucosal immunity, which likely will impair the primary barrier defence against the infection. Systemic IgG responses were also impaired, whereas T-cell responses were normal. Further and larger studies are needed to evaluate the impact of these findings on disease protection.

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Journal of hematology
Journal of hematology HEMATOLOGY-
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