Safety and cross-variant immunogenicity of a three-dose COVID-19 mRNA vaccine regimen in kidney transplant recipients
Filippo Massa, Marion Crémoni, Alexandre O. Gérard, Hanen Grabsi, L.J.J. Rogier, Mathilde Blois, Chloé Couzin, Nadia Ben Hassen, Matthieu Rouleau, Susana Barbosa, Emanuela Martinuzzi, Julien Fayada, Ghislaine Bernard, Guillaume Favre, Paul Hofman, Vincent Esnault, Cécil Czerkinsky, Barbara Seitz‐Polski, Nicolas Glaichenhaus, A Sicard
Abstract
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.