Importance Response to SARS-CoV-2 vaccines in kidney transplant recipients (KTR) is severely reduced. Heterologous 3rd vaccination combining mRNA and vector vaccines did not increase seroconversion at four weeks after vaccination but evolution of antibody levels beyond the first month remain unknown. Objective To assess changes in antibody response following a 3rd vaccination with mRNA or vector vaccine in KTR from month one to month three after vaccination. Design, Setting and Participants Three-month follow-up (pre-specified secondary endpoint) of a single-center, single-blinded, 1:1 randomized, controlled trial on 3rd vaccination against SARS-CoV-2 in 201 KTR who did not develop SARS-CoV-2 spike protein antibodies following two doses of an mRNA vaccine. Intervention(s) mRNA (BNT162b2 or mRNA-1273) or vector (Ad26COVS1) as third SARS-CoV-2 vaccine Main Outcomes and Measures Main outcome was seroconversion at the second follow-up between 60-120 days after the 3rd vaccination. Subsequently, higher cut-off levels associated with neutralizing capacity and protective immunity were applied (i.e. >15, >100, >141 and >264 BAU/mL). In addition, trajectories of antibody levels from month one to month three were analyzed. Finally, SARS-CoV-2 specific CD4 and CD8 T-cells at four weeks were compared among the 18 top responders in both groups. Results A total of 169 patients were available for the three-month follow-up. Overall, seroconversion at three months was similar between both groups (45% versus 50% for mRNA and vector group, respectively; OR=1.24, 95%CI=[0.65, 2.37], p=0.539). However, when applying higher cut-off levels, a significantly larger number of individual in the vector group reached antibody levels > 141 and > 264 BAU/mL at the three-month follow-up (141 BAU/mL: 4% vs. 15% OR=4.96, 95%CI=[1.29, 28.21], p=0.009 and 264 BAU/mL: 1% vs. 10% OR=8.75, 95%CI=[1.13, 396.17], p=0.018 for mRNA vs. vector vaccine group, respectively). In line, antibody levels in seroconverted patients further increased from month one to month three in the vector group while remaining unchanged in the mRNA group (median increase: mRNA= 1.35 U/mL and vector = 27.6 U/mL, p = 0.004). Of particular note, there was no difference in the CD4 and CD8 T-cell response between the mRNA and vector vaccine group at month one. Conclusions and Relevance: Despite a similar overall seroconversion rate at three months following third vaccination in KTR, a heterologous third booster vaccination with Ad26COVS1 resulted in significantly higher antibody levels in responders. Trial Registration: EurdraCT: 2021-002927-39 

The authors have declared no competing interest.

EurdraCT: 2021-002927-39

Medical-Scientific Fund of the Mayor of Vienna, the Christine Vranitzky-Stiftung research grant 2020 (both to Roman Reindl-Schwaighofer) and the Transplantation Research Platform's Start-Up Grant 2020 (to Andreas Heinzel)

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Ethics committee of the Medical University of Vienna gave ethical approval for this work

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