Three-month follow-up of heterologous vs homologous third vaccination in kidney transplant recipients

Abstract

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

Comparison of the Effectiveness and Safety of Heterologous Booster Doses with Homologous Booster Doses for SARS-CoV-2 Vaccines: A Systematic Review and Meta-Analysis

“…Among the 121 studies under full-text review, 98 studies were excluded. Eventually, 23 studies (including 13 published articles and 10 preprints) were included in this meta-analysis based on the inclusion criteria [ 14 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 ]. The literature retrieval flow chart is shown in Figure 1 .…”

“… Risk of bias assessment of the included RCTs [ 14 , 24 , 26 , 27 , 30 , 31 , 35 , 37 , 40 , 41 , 45 ]. …”

A quick scoping review of the first year of vaccination against the COVID-19 pandemic: Do we need more shots or time?

“…In contrast, an increase in neutralizing antibody response induced by a booster dose against Delta [32,48,67] and Omicron [49,68] variants in the general population and immunocompromised patients has been reported by various authors. Immunocompromised patient populations include kidney transplant recipients [53][54][55][56][57][58][59][60][61]66,[68][69][70] and patients undergoing chronic hemodialysis. [51,57,63,74,76] Although >90 vaccines for COVID-19 are under clinical trials, 23 vaccines have been approved for use in different countries in 2021.…”

“…Antibody responses after third or booster dose vaccination among the general population [32,33,39,41,43–45,47–50] and among immunocompromised patients [51–76] have also been evaluated in multiple studies. The waning of immunity against different variants of SARS-CoV-2, such as Delta [16,19,22,25] and Omicron, [28,29] has been reported in several studies.…”

Transplant Moves One Step Closer to Creating a Purpose-Built Organ

“…A new study has found that kidney transplant recipients who receive a heterologous third vaccination combining mRNA and vector SARS‐CoV‐2 vaccines have a seroconversion rate at three months following the third vaccination that is similar to the rate found for a homologous third vaccination. Andreas Heinzel of the Medical University of Vienna in Austria and colleagues found, however, that a heterologous third booster vaccination with the vector vaccine Ad26COVS1 resulted in significantly higher antibody levels in responders 1 …”