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Predictors and Dynamics of the Humoral and Cellular Immune Response to SARS-CoV-2 mRNA Vaccines in Hemodialysis Patients: A Multicenter Observational Study
Journal of the American Society of Nephrology ( IF 10.3 ) Pub Date : 2021-12-01 , DOI: 10.1681/asn.2021070908
Jens Van Praet 1, 2 , Marijke Reynders 3 , Dirk De Bacquer 4 , Liesbeth Viaene 5 , Melanie K Schoutteten 6, 7 , Rogier Caluwé 8 , Peter Doubel 5 , Line Heylen 6, 9 , Annelies V De Bel 10 , Bruno Van Vlem 8 , Deborah Steensels 11 , An S De Vriese 1, 2
Affiliation  

Background

Preliminary evidence suggests patients on hemodialysis have a blunted early serological response to SARS-CoV-2 vaccination. Optimizing the vaccination strategy in this population requires a thorough understanding of predictors and dynamics of humoral and cellular immune responses to different SARS-CoV-2 vaccines.

Methods

This prospective multicenter study of 543 patients on hemodialysis and 75 healthy volunteers evaluated the immune responses at 4 or 5 weeks and 8 or 9 weeks after administration of the BNT162b2 or mRNA-1273 vaccine, respectively. We assessed anti–SARS-CoV-2 spike antibodies and T cell responses by IFN- secretion of peripheral blood lymphocytes upon SARS-CoV-2 glycoprotein stimulation (QuantiFERON assay) and evaluated potential predictors of the responses.

Results

Compared with healthy volunteers, patients on hemodialysis had an incomplete, delayed humoral immune response and a blunted cellular immune response. Geometric mean antibody titers at both time points were significantly greater in patients vaccinated with mRNA-1273 versus BNT162b2, and a larger proportion of them achieved the threshold of 4160 AU/ml, corresponding with high neutralizing antibody titers in vitro (53.6% versus 31.8% at 8 or 9 weeks, P<0.0001). Patients vaccinated with mRNA-1273 versus BNT162b2 exhibited significantly greater median QuantiFERON responses at both time points, and a larger proportion achieved the threshold of 0.15 IU/ml (64.4% versus 46.9% at 8 or 9 weeks, P<0.0001). Multivariate analysis identified COVID-19 experience, vaccine type, use of immunosuppressive drugs, serum albumin, lymphocyte count, hepatitis B vaccine nonresponder status, and dialysis vintage as independent predictors of the humoral and cellular responses.

Conclusions

The mRNA-1273 vaccine’s greater immunogenicity may be related to its higher mRNA dose. This suggests a high-dose vaccine might improve the impaired immune response to SARS-CoV-2 vaccination in patients on hemodialysis.



中文翻译:

血液透析患者对 SARS-CoV-2 mRNA 疫苗的体液和细胞免疫反应的预测因子和动力学:一项多中心观察研究

背景

初步证据表明接受血液透析的患者对 SARS-CoV-2 疫苗接种的早期血清学反应减弱。优化这一人群的疫苗接种策略需要透彻了解对不同 SARS-CoV-2 疫苗的体液和细胞免疫反应的预测因子和动态。

方法

这项针对 543 名血液透析患者和 75 名健康志愿者的前瞻性多中心研究分别评估了接种 BNT162b2 或 mRNA-1273 疫苗后 4 或 5 周和 8 或 9 周时的免疫反应。我们通过 SARS-CoV-2 糖蛋白刺激(QuantiFERON 测定)后外周血淋巴细胞的 IFN- 分泌评估了抗 SARS-CoV-2 刺突抗体和 T 细胞反应,并评估了反应的潜在预测因子。

结果

与健康志愿者相比,血液透析患者的体液免疫反应不完全、延迟,细胞免疫反应减弱。接种 mRNA-1273 疫苗的患者与接种 BNT162b2 疫苗的患者在两个时间点的几何平均抗体滴度均显着更高,其中更大比例达到 4160 AU/ml 的阈值,对应于体外高中和抗体滴度(53.6% 对 31.8% )在 8 或 9 周时,P <0.0001)。与 BNT162b2 相比,接种 mRNA-1273 的患者在两个时间点都表现出明显更高的 QuantiFERON 反应中值,并且更大比例的患者达到了 0.15 IU/ml 的阈值(8 周或 9 周时分别​​为 64.4% 和 46.9%,P<0.0001)。多变量分析确定了 COVID-19 经验、疫苗类型、免疫抑制药物的使用、血清白蛋白、淋巴细胞计数、乙型肝炎疫苗无反应状态和透析年份作为体液和细胞反应的独立预测因子。

结论

mRNA-1273 疫苗更强的免疫原性可能与其更高的 mRNA 剂量有关。这表明高剂量疫苗可能会改善接受血液透析的患者对 SARS-CoV-2 疫苗接种受损的免疫反应。

更新日期:2021-11-30
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