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. We report the first complete assessment safety and cross-variant three-dose KT recipients. Methods: performed prospective longitudinal study sixty-one recipients given three doses BNT162b2 vaccine. semi-structured pharmacovigilance interviews monitored donor-specific antibodies function. compared geometric mean titers (GMT) anti-spike IgG, pseudo-neutralization activity against homologous heterologous variants, frequency spike-specific interferon (IFN)-γ-secreting cells, antigen-induced cytokine production 28 days after second third doses. immunoassays were also non-transplanted individuals dose to obtain reference values. Findings: Reactions mild. One patient developed anti-HLA which could be explained by non-adherence immunosuppressive therapy. Spike-specific IgG seroconversion raised from 44·3% (n=27) 62·3% (n=38) (p<0·05). GMT increased 528·3 (95% CI 300·0-930·1) 2395 AU/ml CI 1214-4724, p<0·0001). Serum neutralizing 4·7% 17·2% (Wuhan strain), 4·0% 17·4% (alpha variant), 2·3% 7·3% (beta 1·3% 9·1% (gamma variant) (p<0·0001), remained lower than values. IFN-γ-secreting cells 19·9 (SD 56·0) 64·0 76·8) cells/million PBMCs (p<0·0001). A significant increase IFN-γ responses was observed patients who seronegative (p<0·0001). Interpretation: increases both SARS-CoV-2-specific humoral cellular with an acceptable tolerability profile. However, antibody titres remain doses, especially variants concern, barrier measures vaccination relatives essential. Funding Information: This work supported grants Nice University Hospital (AOI) Cote d’Azur (IDEX). Declaration Interests: authors declare no competing interests. Ethics Approval Statement: protocol complies principles Declaration Helsinki approved our institutional committee. Written informed consent obtained all participants collected data samples anonymized securely stored.