血液系统恶性肿瘤患者对SARS-CoV-2疫苗的免疫原性较弱
Weak immunogenicity of SARS-CoV-2 vaccine in patients with hematologic malignancies
原文发布日期:2021-08-10
DOI: 10.1038/s41408-021-00534-z
类型: Article
开放获取: 是
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This study evaluated the safety and immunogenicity of BNT162b2 vaccine in patients with hematological malignancies. Antibodies blocking spike binding to immobilized ACE-2 (NAb) correlated with anti-Spike (S) IgG d42 titers (Spearman r = 0.865, p < 0.0001), and an anti-S IgG d42 level ≥3100 UA/mL was predictive of NAb ≥ 30%, the positivity cutoff for NAb (p < 0.0001). Only 47% of the patients achieved an anti-S IgG d42 level ≥3100 UA/mL after the two BNT162b2 inocula, compared to 87% of healthy controls. In multivariable analysis, male patients, use of B-cell targeting treatment within the last 12 months prior to vaccination, and CD19+ B-cell level <120/uL, were associated with a significantly decreased probability of achieving a protective anti-S IgG level after the second BNT162b2 inoculum. Finally, using the IFN-γ ELISPOT assay, we found a significant increase in T-cell response against the S protein, with 53% of patients having an anti-S IgG-positive ELISPOT after the second BNT162b2 inoculum. There was a correlation between the anti-S ELISPOT response and IgG d42 level (Spearman r = 0.3026, p = 0.012). These findings suggest that vaccination with two BNT162b2 inocula translates into a significant increase in humoral and cellular response in patients with hematological malignancies, but only around half of the patients can likely achieve effective immune protection against COVID-19.
本研究评估了BNT162b2疫苗在血液系统恶性肿瘤患者中的安全性和免疫原性。阻断刺突蛋白与固定化血管紧张素转换酶2结合的中和抗体与抗刺突蛋白IgG接种后42天的抗体滴度相关(Spearman r=0.865,p<0.0001),且抗刺突蛋白IgG接种后42天水平≥3100 UA/mL可预测中和抗体≥30%(中和抗体阳性阈值,p<0.0001)。仅47%的患者在两次BNT162b2接种后达到抗刺突蛋白IgG水平≥3100 UA/mL,而健康对照组达87%。多变量分析显示,男性患者、接种前12个月内接受过B细胞靶向治疗以及CD19+ B细胞水平<120/μL,与第二次BNT162b2接种后获得保护性抗刺突蛋白IgG水平的概率显著降低相关。最后,通过干扰素-γ酶联免疫斑点法检测,我们发现针对刺突蛋白的T细胞反应显著增强,53%的患者在第二次BNT162b2接种后出现抗刺突蛋白IgG阳性斑点反应。抗刺突蛋白斑点反应与IgG接种后42天水平存在相关性(Spearman r=0.3026,p=0.012)。这些结果表明,两次BNT162b2接种能显著提升血液系统恶性肿瘤患者的体液和细胞免疫反应,但仅约半数患者可能实现对新冠肺炎的有效免疫保护。
Weak immunogenicity of SARS-CoV-2 vaccine in patients with hematologic malignancies
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