Aims

Immunocompromised patients have been excluded from studies of SARS-CoV-2 messenger RNA vaccines. The immune response to vaccines against other infectious agents has been shown to be blunted in such patients. We aimed to analyse the humoral and cellular response to prime-boost vaccination with the BNT162b2 vaccine (Pfizer-BioNTech) in cardiothoracic transplant recipients.

Methods and results

A total of 50 transplant patients [1–3 years post heart (42), lung (7), or heart–lung (1) transplant, mean age 55 ± 10 years] and a control group of 50 healthy staff members were included. Blood samples were analysed 21 days after the prime and the boosting dose, respectively, to quantify anti-SARS-CoV-2 spike protein (S) immunoglobulin titres (tested by Abbott, Euroimmun and RocheElecsys Immunoassays, each) and the functional inhibitory capacity of neutralizing antibodies (Genscript). To test for a specific T-cell response, heparinized whole blood was stimulated with SARS-CoV-2 specific peptides, covering domains of the viral spike, nucleocapsid and membrane protein, and the interferon-γ release was measured (QuantiFERON Monitor ELISA, Qiagen). The vast majority of transplant patients (90%) showed neither a detectable humoral nor a T-cell response three weeks after the completed two-dose BNT162b2 vaccination; these results are in sharp contrast to the robust immunogenicity seen in the control group: 98% exhibited seroconversion after the prime dose already, with a further significant increase of IgG titres after the booster dose (average > tenfold increase), a more than 90% inhibition capability of neutralizing antibodies as well as evidence of a T-cell responsiveness.

Conclusions

The findings of poor immune responses to a two-dose BNT162b2 vaccination in cardiothoracic transplant patients have a significant impact for organ transplant recipients specifically and possibly for immunocompromised patients in general. It urges for a review of future vaccine strategies in these patients.

中文翻译：

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心胸移植受者对两剂 SARS-CoV-2 信使 RNA 疫苗 BNT162b2 的体液和 T 细胞反应较差

目标

免疫功能低下的患者已被排除在 SARS-CoV-2 信使 RNA 疫苗的研究之外。此类患者对针对其他传染源的疫苗的免疫反应已被证明减弱。我们的目的是分析心胸移植受者对 BNT162b2 疫苗 (Pfizer-BioNTech) 初免加强疫苗接种的体液和细胞反应。

方法和结果

总共包括 50 名移植患者 [心脏 (42)、肺 (7) 或心肺 (1) 移植后 1-3 年，平均年龄 55 ± 10 岁] 和由 50 名健康工作人员组成的对照组。分别在初免剂量和加强剂量后 21 天对血液样本进行分析，以量化抗 SARS-CoV-2 刺突蛋白 (S) 免疫球蛋白滴度（分别由 Abbott、Euroimmun 和 RocheElecsys 免疫测定法进行测试）和功能抑制能力中和抗体（Genscript）。为了测试特定的 T 细胞反应，用 SARS-CoV-2 特异性肽刺激肝素化全血，涵盖病毒刺突、核衣壳和膜蛋白的结构域，并测量干扰素-γ 释放（QuantiFERON Monitor ELISA，Qiagen） ）。绝大多数移植患者 (90%) 在完成两剂 BNT162b2 疫苗接种后三周既没有表现出可检测到的体液反应，也没有显示出 T 细胞反应；这些结果与对照组中观察到的强大免疫原性形成鲜明对比：98% 在初免剂量后已表现出血清转化，在加强剂量后 IgG 滴度进一步显着增加（平均增加十倍以上），超过 90%中和抗体的抑制能力以及 T 细胞反应性的证据。

结论

心胸移植患者对两剂 BNT162b2 疫苗接种的免疫反应不佳的发现对器官移植受者特别是对一般免疫功能低下的患者有重大影响。它敦促对这些患者未来的疫苗策略进行审查。