EBioMedicine (Nov 2021)

Safety and Cross-Variant Immunogenicity of a Three-dose COVID-19 mRNA Vaccine Regimen in Kidney Transplant Recipients

  • Filippo Massa, PhD,
  • Marion Cremoni, MD,
  • Alexandre Gérard, MD,
  • Hanen Grabsi,
  • Lory Rogier,
  • Mathilde Blois, MD,
  • Chloé Couzin, MD,
  • Nadia Ben Hassen,
  • Matthieu Rouleau, PhD,
  • Susana Barbosa, PhD,
  • Emanuela Martinuzzi, PhD,
  • Julien Fayada,
  • Ghislaine Bernard, MD-PhD,
  • Guillaume Favre, MD-PhD,
  • Paul Hofman, MD-PhD,
  • Vincent L.M. Esnault, MD-PhD,
  • Cecil Czerkinsky, MD-PhD,
  • Barbara Seitz-Polski, MD-PhD,
  • Nicolas Glaichenhaus, PhD,
  • Antoine Sicard, MD-PhD

Journal volume & issue
Vol. 73
p. 103679

Abstract

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Background: 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. Methods: 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. Findings: 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). Interpretation: A third dose of the BNT162b2 vaccine increases both cross-variant neutralizing antibody and cellular responses in KT recipients with an acceptable tolerability profile. Funding: Nice University Hospital, University Cote d'Azur.

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