B and T Cell Responses after a Third Dose of SARS-CoV-2 Vaccine in Kidney Transplant Recipients

Significance statement Protection of solid organ transplant recipients against SARS-CoV-2 by vaccination remains an unmet need, given the low immunogenicity of available vaccines in the presence of immunosuppression. Administration of a third dose to 25 kidney transplant recipients (KTR) resulted in seroconversion in 36% of patients, associated with significant quantitative and functional changes within the spike-antigen?specific B cell and CD4(+) T-helper cell compartment. Our data support the need for individual humoral monitoring of immunosuppressed individuals after vaccination and continued efforts to adapt vaccination protocols for this at-risk group. Background Accumulating evidence sugges ts solid organ transplant recipients, as opposed to the general population, show strongly impaired responsiveness toward standard SARS-CoV-2 mRNA-based vaccination, demanding alternative strategies for protectio n o f this vulnerable group. Methods In line with recent recommendations, a third dose of either heterologous ChAdOx1 (AstraZeneca) or homologous BNT162b2 (BioNTech) was administered to 25 kidney transplant recipients (KTR) without humoral response after two doses of BNT162b2, followed by analysis of serological responses and vaccine-specific B- and T-cell immunity. Results Nine out of 25 (36%) KTR under standard immunosuppressive treatment seroconverted until day 27 after the third vaccination, whereas one patient developed severe COVID-19 infection immediately after vaccination. Cellular analysis 7 days after the third dose showed significantly elevated frequencies of viral spike-protein receptor-binding domain-specific B cells in humor al responders as compared with nonresponders. Likewise, portions of spike-reactive CD4(+) T helper cells were significantly elevated in patients who were seroconverting. Furthermore, overall frequencies of IL-2(+), IL-4(+), and polyfunctional CD4(+) T cells significantly increased after the third dose, whereas memory/effector differentiation remained unaffected. Conclusions Our data suggest a fraction of transplant recipients benefit from triple vaccination, where seroconversion is associated with quantitative and qualitative changes of cellular immunity. At the same time, the study highlights that modified vaccination approaches for immunosuppressed patients remain an urgent medical need. Podcast This article contains a podcast athttps://www.asn-online.org/media/podcast/JASN/2021_11_23_briggsgriffin112321.mp3