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

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)-gamma-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-gamma-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-gamma 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. (C) 2021 Published by Elsevier B.V.

Automated summary

A three-dose regimen of the BNT162b2 COVID-19 vaccine significantly improves anti-spike IgG levels, neutralizing antibodies, and cellular immune responses in kidney transplant recipients with a tolerable tolerability profile.