Frontiers in Medicine (Aug 2022)

Humoral response to SARS-CoV-2 mRNA vaccination in previous non-responder kidney transplant recipients after short-term withdrawal of mycophenolic acid

  • Louise Benning,
  • Christian Morath,
  • Tessa Kühn,
  • Marie Bartenschlager,
  • Heeyoung Kim,
  • Jörg Beimler,
  • Mirabel Buylaert,
  • Christian Nusshag,
  • Florian Kälble,
  • Marvin Reineke,
  • Maximilian Töllner,
  • Matthias Schaier,
  • Katrin Klein,
  • Antje Blank,
  • Antje Blank,
  • Paul Schnitzler,
  • Martin Zeier,
  • Caner Süsal,
  • Ralf Bartenschlager,
  • Ralf Bartenschlager,
  • Ralf Bartenschlager,
  • Thuong Hien Tran,
  • Claudius Speer,
  • Claudius Speer

DOI
https://doi.org/10.3389/fmed.2022.958293
Journal volume & issue
Vol. 9

Abstract

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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 Mycophenolic acid was withdrawn in 43 selected patients 5–7 days prior to vaccination and remained paused for 4 additional weeks after vaccination.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 The effect was most pronounced in individuals in whom mycophenolic acid was withdrawn during vaccination.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.

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