Safety and cross-variant immunogenicity of a three-dose COVID-19 mRNA vaccine regimen in kidney transplant recipients

EBioMedicine. 2021 Nov;73:103679. doi: 10.1016/j.ebiom.2021.103679. Epub 2021 Nov 8.


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.

Keywords: COVID-19; Immunogenicity; mRNA vaccine; variants of concern, kidney transplantation.

MeSH terms

  • Aged
  • Antibodies, Neutralizing / blood
  • Antibodies, Neutralizing / immunology*
  • Autoantibodies / blood
  • BNT162 Vaccine / administration & dosage
  • BNT162 Vaccine / adverse effects
  • BNT162 Vaccine / immunology*
  • COVID-19 / immunology*
  • COVID-19 / prevention & control
  • COVID-19 / virology
  • Female
  • Graft Rejection / prevention & control
  • HLA Antigens / immunology
  • Humans
  • Immunoglobulin G / blood
  • Immunoglobulin G / immunology
  • Immunosuppressive Agents / therapeutic use
  • Interferon-gamma / metabolism
  • Kidney Transplantation*
  • Leukocytes, Mononuclear / cytology
  • Leukocytes, Mononuclear / metabolism
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Risk Factors
  • SARS-CoV-2 / immunology
  • SARS-CoV-2 / isolation & purification
  • SARS-CoV-2 / metabolism
  • Spike Glycoprotein, Coronavirus / immunology


  • Antibodies, Neutralizing
  • Autoantibodies
  • HLA Antigens
  • Immunoglobulin G
  • Immunosuppressive Agents
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2
  • Interferon-gamma
  • BNT162 Vaccine

Supplementary concepts

  • SARS-CoV-2 variants