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.
Keywords: COVID-19; Immunogenicity; mRNA vaccine; variants of concern, kidney transplantation.
【저자키워드】 COVID-19, immunogenicity, mRNA vaccine, variants of concern, kidney transplantation., 【초록키워드】 neutralizing antibody, IgG, Vaccine, BNT162b2 vaccine, COVID-19 vaccine, immunogenicity, therapy, antibody, mRNA vaccine, Kidney function, variants of concern, interferon, cytokine, delta variant, variants, Antigen, kidney, BNT162b2, Neutralizing activity, Seroconversion, anti-Spike IgG, cells, longitudinal study, mRNA, Patient, Mild, PBMC, homologous, university, seronegative, cytokine production, Heterologous, kidney transplant, IFN-γ, immunosuppressive therapy, cellular response, Frequency, dose, PBMCs, immunosuppressive, Cellular responses, regimen, Tolerability, Reactions, reaction, recipients, second dose, significant increase, one patient, neutralization activity, doses, recipient, spike-specific IgG, Cell, IFN-γ responses, Nice University Hospital, tested, performed, remained, raised, increase, explained, IFN-γ response, 【제목키워드】 Safety, kidney transplant recipient, regimen,