Töllner Maximilian, Speer Claudius, Benning Louise, Bartenschlager Marie, Nusshag Christian, Morath Christian, Zeier Martin, Süsal Caner, Schnitzler Paul, Schmitt Wilhelm, Bergner Raoul, Bartenschlager Ralf, Lorenz Hanns-Martin, Schaier Matthias
Department of Nephrology, University of Heidelberg, 69120 Heidelberg, Germany.
Molecular Medicine Partnership Unit Heidelberg, European Molecular Biology Laboratory, 69120 Heidelberg, Germany.
J Clin Med. 2022 Mar 21;11(6):1739. doi: 10.3390/jcm11061739.
Background: To characterize humoral response after standard anti-SARS-CoV-2 vaccination in Rituximab-treated patients and to determine the optimal time point after last Rituximab treatment for appropriate immunization. Methods: Sixty-four patients who received Rituximab within the last seven years prior to the first anti-SARS-CoV-2 vaccination were recruited in a prospective observational study. Anti-S1 IgG, SARS-CoV-2 specific neutralization, and various SARS-CoV-2 target antibodies were determined. A live virus assay was used to assess neutralizing antibody activity against B.1.617.2 (delta). In Rituximab-treated patients, CD19+ peripheral B-cells were quantified using flow cytometry. Results: After second vaccination, all antibodies were significantly reduced compared to healthy controls. Neutralizing antibody activity against B.1.617.2 (delta) was detectable with a median (IQR) ID50 of 0 (0−1:20) compared to 1:320 (1:160−1:320) in healthy controls (for all p < 0.001). Longer time period since last Rituximab administration correlated with higher anti-SARS-CoV-2 antibody levels and a stronger neutralization of B.1.617.2 (delta). With one exception, only patients with a CD19+ cell proportion ≥ 1% had detectable neutralizing antibodies. Conclusion: Our data indicate that a reconstitution of the B-cell population to >1% seems crucial in developing neutralizing antibodies against SARS-CoV-2. We suggest that anti-SARS-CoV-2 vaccination should be administered at least 8−12 months after the last Rituximab treatment for sufficient humoral responses.
描述接受利妥昔单抗治疗的患者在接种标准抗SARS-CoV-2疫苗后的体液反应，并确定最后一次利妥昔单抗治疗后进行适当免疫的最佳时间点。方法：在一项前瞻性观察性研究中招募了64例在首次抗SARS-CoV-2疫苗接种前7年内接受过利妥昔单抗治疗的患者。测定抗S1 IgG、SARS-CoV-2特异性中和抗体以及各种SARS-CoV-2靶标抗体。采用活病毒试验评估针对B.1.617.2（德尔塔）的中和抗体活性。在接受利妥昔单抗治疗的患者中，使用流式细胞术对CD19+外周B细胞进行定量。结果：与健康对照相比，第二次接种疫苗后所有抗体均显著降低。针对B.1.617.2（德尔塔）的中和抗体活性可检测到，中位（IQR）ID50为0（0−1:20），而健康对照为1:320（1:160−1:320）（所有p<0.001）。自上次利妥昔单抗给药以来的时间越长，抗SARS-CoV-2抗体水平越高，对B.1.617.2（德尔塔）的中和作用越强。除一例例外，只有CD19+细胞比例≥1%的患者可检测到中和抗体。结论：我们的数据表明，B细胞群体重建至>1%似乎对于产生针对SARS-CoV-2的中和抗体至关重要。我们建议，为了获得足够的体液反应，抗SARS-CoV-2疫苗应在最后一次利妥昔单抗治疗后至少8−12个月接种。
