Benning Louise, Morath Christian, Kühn Tessa, Bartenschlager Marie, Kim Heeyoung, Beimler Jörg, Buylaert Mirabel, Nusshag Christian, Kälble Florian, Reineke Marvin, Töllner Maximilian, Schaier Matthias, Klein Katrin, Blank Antje, Schnitzler Paul, Zeier Martin, Süsal Caner, Bartenschlager Ralf, Tran Thuong Hien, Speer Claudius
Department of Nephrology, University of Heidelberg, Heidelberg, Germany.
Department of Infectious Diseases, Molecular Virology, University of Heidelberg, Heidelberg, Germany.
Front Med (Lausanne). 2022 Aug 18;9:958293. doi: 10.3389/fmed.2022.958293. eCollection 2022.
Seroconversion rates after COVID-19 vaccination are significantly lower in kidney transplant recipients compared to healthy cohorts. Adaptive immunization strategies are needed to protect these patients from COVID-19. In this prospective observational cohort study, we enrolled 76 kidney transplant recipients with no seroresponse after at least three COVID-19 vaccinations to receive an additional mRNA-1273 vaccination (full dose, 100 μg). Mycophenolic acid was withdrawn in 43 selected patients 5-7 days prior to vaccination and remained paused for 4 additional weeks after vaccination. SARS-CoV-2-specific antibodies and neutralization of the delta and omicron variants were determined using a live-virus assay 4 weeks after vaccination. In patients with temporary mycophenolic acid withdrawal, donor-specific anti-HLA antibodies and donor-derived cell-free DNA were monitored before withdrawal and at follow-up. SARS-CoV-2 specific antibodies significantly increased in kidney transplant recipients after additional COVID-19 vaccination. The effect was most pronounced in individuals in whom mycophenolic acid was withdrawn during vaccination. Higher SARS-CoV-2 specific antibody titers were associated with better neutralization of SARS-CoV-2 delta and omicron variants. In patients with short-term withdrawal of mycophenolic acid, graft function and donor-derived cell-free DNA remained stable. No acute rejection episode occurred during short-term follow-up. However, resurgence of prior anti-HLA donor-specific antibodies was detected in 7 patients.
与健康人群相比，肾移植受者在接种新冠疫苗后的血清转化发生率显著更低。需要采取适应性免疫策略来保护这些患者免受新冠病毒感染。在这项前瞻性观察队列研究中，我们招募了76名在至少接种三剂新冠疫苗后仍无血清反应的肾移植受者，让他们额外接种一剂mRNA-1273疫苗（全剂量，100μg）。43名选定患者在接种疫苗前5至7天停用霉酚酸，并在接种疫苗后再暂停4周。在接种疫苗4周后，使用活病毒检测法测定新冠病毒特异性抗体以及对德尔塔和奥密克戎变异株的中和能力。在暂时停用霉酚酸的患者中，在停药前和随访时监测供者特异性抗HLA抗体和供者来源的游离DNA。在肾移植受者额外接种新冠疫苗后，新冠病毒特异性抗体显著增加。这种效果在接种疫苗期间停用霉酚酸的个体中最为明显。更高的新冠病毒特异性抗体滴度与对新冠病毒德尔塔和奥密克戎变异株更好的中和能力相关。在短期停用霉酚酸的患者中，移植肾功能和供者来源的游离DNA保持稳定。在短期随访期间未发生急性排斥反应。然而，在7名患者中检测到既往抗HLA供者特异性抗体复现。
