Department of Nephrology, Dialysis and Transplantation, Pasteur 2 Hospital, Nice University Hospital, 30 voie Romaine, 06300, Nice, France; Laboratory of Molecular Physio Medicine, University Côte d'Azur, CNRS, 28 Avenue de Valombrose, 06107, Nice, France; Clinical Research Unit Côte d'Azur (UR2CA), University Côte d'Azur, 28 Avenue de Valombrose, 06107, Nice, France.
Department of Nephrology, Dialysis and Transplantation, Pasteur 2 Hospital, Nice University Hospital, 30 voie Romaine, 06300, Nice, France; Clinical Research Unit Côte d'Azur (UR2CA), University Côte d'Azur, 28 Avenue de Valombrose, 06107, Nice, France.
EBioMedicine. 2021 Nov;73:103679. doi: 10.1016/j.ebiom.2021.103679. Epub 2021 Nov 8.
The immunogenicity of a two-dose mRNA COVID-19 vaccine regimen is low in kidney transplant (KT) recipients. Here, we provide a thorough assessment of the immunogenicity of a three-dose COVID-19 vaccine regimen in this population.
We performed a prospective longitudinal study in sixty-one KT recipients given three doses of the BNT162b2 COVID-19 vaccine. We performed semi-structured pharmacovigilance interviews and monitored donor-specific antibodies and kidney function. We compared levels of anti-spike IgG, pseudo-neutralization activity against vaccine homologous and heterologous variants, frequency of spike-specific interferon (IFN)-γ-secreting cells, and antigen-induced cytokine production 28 days after the second and third doses.
Reactions to vaccine were mild. One patient developed donor-specific anti-HLA antibodies after the second dose which could be explained by non-adherence to immunosuppressive therapy. Spike-specific IgG seroconversion raised from 44·3% (n=27) after the second dose to 62·3% (n=38) after the third dose (p<0·05). The mean level of spike-specific IgG increased from 1620 (SD, 3460) to 8772 (SD, 16733) AU/ml (p<0·0001). Serum neutralizing activity increased after the third dose for all variants of concern tested including the Delta variant (p<0·0001). The frequency of spike-specific IFN-γ-secreting cells increased from 19·9 (SD, 56·0) to 64·0 (SD, 76·8) cells/million PBMCs after the third dose (p<0·0001). A significant increase in IFN-γ responses was also observed in patients who remained seronegative after three doses (p<0·0001).
A third dose of the BNT162b2 vaccine increases both cross-variant neutralizing antibody and cellular responses in KT recipients with an acceptable tolerability profile.
Nice University Hospital, University Cote d'Azur.
两剂 mRNA COVID-19 疫苗方案在肾移植 (KT) 受者中的免疫原性较低。在这里，我们提供了对该人群三剂 COVID-19 疫苗方案免疫原性的全面评估。
我们对 61 名接受三剂 BNT162b2 COVID-19 疫苗的 KT 受者进行了前瞻性纵向研究。我们进行了半结构式药物警戒访谈，并监测了供体特异性抗体和肾功能。我们比较了第二剂和第三剂后 28 天抗刺突 IgG 水平、对疫苗同源和异源变体的假中和活性、刺突特异性干扰素 (IFN)-γ 分泌细胞的频率以及抗原诱导的细胞因子产生。
疫苗反应轻微。一名患者在第二剂后出现供体特异性抗 HLA 抗体，这可能是由于免疫抑制治疗不依从所致。第二剂后刺突特异性 IgG 血清转化率从 44.3%（n=27）升高至 62.3%（n=38）（p<0.05）。刺突特异性 IgG 水平均值从 1620（SD，3460）升高至 8772（SD，16733）AU/ml（p<0.0001）。第三剂后，所有测试的关注变体（包括 Delta 变体）的血清中和活性均增加（p<0.0001）。第三剂后，刺突特异性 IFN-γ 分泌细胞的频率从 19.9（SD，56.0）增加至 64.0（SD，76.8）细胞/百万 PBMCs（p<0.0001）。在三剂后仍呈血清阴性的患者中也观察到 IFN-γ 反应显著增加（p<0.0001）。
第三剂 BNT162b2 疫苗可增加 KT 受者的跨变体中和抗体和细胞反应，且具有可接受的耐受性特征。
尼斯大学医院，蔚蓝海岸大学。
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