Comparison of SARS-CoV-2 Antibody Response 4 Weeks After Homologous vs Heterologous Third Vaccine Dose in Kidney Transplant Recipients

Reindl‐Schwaighofer, Roman; Heinzel, Andreas; Mayrdorfer, Manuel; Jabbour, Rhea; Hofbauer, Thomas M.; Merrelaar, Anne; Eder, Michael; Regele, Florina; Doberer, Konstantin; Spechtl, Paul; Aschauer, Constantin; Koblischke, Maximilian; Paschen, Christopher; Eskandary, Farsad; Hu, Karin; Öhler, Barbara; Bhandal, Arshdeep; Kleibenböck, Sabine; Jagoditsch, Rahel I; Reiskopf, Bianca; Heger, Florian; Bond, Gregor; Böhmig, Georg A.; Straßl, Robert; Weseslindtner, Lukas; Indra, Alexander; Aberle, Judith H.; Binder, Michael; Oberbauer, Rainer

doi:10.1001/jamainternmed.2021.7372

Cited by 113 publications

(147 citation statements)

References 36 publications

(62 reference statements)

Supporting

Mentioning

124

Contrasting

Order By: Relevance

“…Indeed, recent data suggested that a third dose COVID-19 vaccine could increase the seropositivity rate from 40 to 68% in KTRs with no serious adverse events reported ( 43 ). Heterologous vaccination strategy with a third dose being a vector-based vaccine demonstrated comparable immunogenicity and safety to that of mRNA vaccine among KTRs who remained seronegative after 2 doses of mRNA vaccine ( 44 ). Furthermore, based on the experience of using intradermal route or adjuvants for HBV and influenza vaccines in immunocompromised hosts ( 45 ), it is also worthwhile to investigate whether these approaches may potentially enhance the immunogenicity and clinical efficacy of COVID-19 vaccines in KTRs.…”

Section: Discussionmentioning

confidence: 99%

Immunogenicity and Safety of COVID-19 Vaccines in Patients Receiving Renal Replacement Therapy: A Systematic Review and Meta-Analysis

et al. 2022

View full text Add to dashboard Cite

BackgroundSystematic data on the efficacy and safety of COVID-19 vaccine in patients on renal replacement therapy (RRT) remains limited. We conducted a meta-analysis on the efficacy and safety of COVID-19 vaccine in patients on RRT.MethodsEligible studies were identified by systematic literature search in four electronic databases. Twenty-seven studies (4,264 patients) were included for meta-analysis. 99% patients received mRNA vaccine.ResultsPatients on RRT showed inferior seropositivity after two-dosed COVID-19 vaccine, 44% lower than the general population. Kidney transplant recipients (KTRs) had significantly lower seropositivity than patients on haemodialysis (HD) or peritoneal dialysis (PD) (26.1 vs. 84.3% and 92.4% respectively, p < 0.001 for both). Compared with healthy controls, KTRs, HD and PD patients were 80% (95% CI: 62–99%), 18% (95% CI: 9–27%) and 11% (95% CI: 1–21%) less likely to develop antibodies after vaccination (p < 0.001, <0.001 and 0.39 respectively). In KTRs, every 1% increase in using mycophenolate was associated with 0.92% reduction in seropositivity (95% CI: −1.68, −0.17, p = 0.021) at population level. The overall adverse event rate attributed to vaccination was 2.1%. Most events were mild.ConclusionPatients on RRT, particularly KTRs, had significantly reduced antibody response after two-dosed COVID-19 vaccination. Vaccination is generally well tolerated.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/, identifier: CRD42021261879.

show abstract

Section: Discussionmentioning

confidence: 99%

Immunogenicity and Safety of COVID-19 Vaccines in Patients Receiving Renal Replacement Therapy: A Systematic Review and Meta-Analysis

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Details on randomization and treatment have been reported before. 3 In short: 200 patients without detectable SARS-CoV-2 specific antibodies following two doses of an mRNA vaccine were randomized to a 3 rd dose of the same mRNA vaccine (mRNA group) or a dose of the vector vaccine Ad26COVS1. Clinical endpoints (death, COVID-19) were recorded for all study participants throughout the observation period.…”

Section: Methodsmentioning

confidence: 99%

“…We recently conducted a randomized single-blinded controlled trial in 200 patients comparing a homologous vs heterologous vaccination strategy in KTR who did not develop SARS-CoV-2 spike protein-specific antibodies after two doses of an mRNA vaccine: Overall, 39% of patients developed antibodies at four weeks after the 3 rd dose, with no statistically significant difference between an additional dose of the same mRNA vaccine as used for the initial prime/boost vaccination (BNT162b2 or mRNA-1273, 35% response rate) or a vector vaccine (Ad26COVS1, 42% response rate). 3 Other recent reports, however, suggest a more pronounced induction of both, a SARS-CoV-2 specific CD4 T cell response and antibodies following heterologous vaccination that includes a vector-based vaccine in transplant recipients. 4 In line, heterologous 3 rd vaccination also increased overall T-cell response in patients treated with B-cell depleting therapy.…”

Section: Introductionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

Heinzel

Schrezenmeier

Regele

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

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

show abstract

“…The detected levels of neutralizing antibodies have been shown to be higher after administration of the BioNTech/Pfizer vaccine BNT162b2 than those after receiving the AstraZeneca vaccine ChAdOx1, although this could not be shown for T-cell responses [13]. These differences have led to the discussion regarding potential benefit from a heterologous vaccination strategy [13][14][15][16].…”

Section: Introductionmentioning

confidence: 99%

Cellular and humoral immune response to a third dose of BNT162b2 COVID-19 vaccine – a prospective observational study

Herzberg

Fischer

Becher

et al. 2022

Preprint

View full text Add to dashboard Cite

Background Since the introduction of various vaccines against SARS-CoV-2 at the end of 2020, rates of infection have continued to climb worldwide. This led to the establishment of a third dose vaccination in several countries, known as a booster. To date, there has been little real-world data about the immunological effect of this strategy. Methods We compared the humoral- and cellular immune response before and after the third dose of BioNTech/Pfizer vaccine BNT162b2, following different prime-boost regimes. Humoral immunity was assessed by determining anti-SARS-CoV-2 binding antibodies using a standardized quantitative assay. In addition, neutralizing antibodies were measured using a commercial surrogate ELISA-assay. Interferon-gamma release was measured after stimulating blood-cells with SARS-CoV-2 specific peptides using a commercial assay to evaluate the cellular immune response. Results The median antibody level increased significantly after the third dose to 2663.1 BAU/ml vs. 101.4 BAU/ml (p < 0.001) before administration of the boosting dose. This was also detected for neutralizing antibodies with a binding inhibition of 99.68% ± 0.36% vs. 69.06% ± 19.88% after the second dose (p < 0.001). 96.3% of the participants showed a detectable T-cell-response after the third dose with a mean interferon-gamma level of 2207.07 mIU/ml ± 1905 mIU/ml. Conclusion This study detected a BMI-dependent increase after the third dose of BNT162b2 following different vaccination protocols, whereas all participants showed a significant increase of their immune response. This, in combination with the limited post-vaccination-symptoms underlines the potential beneficial effect of a BNT162b2-boosting dose.

show abstract

Comparison of SARS-CoV-2 Antibody Response 4 Weeks After Homologous vs Heterologous Third Vaccine Dose in Kidney Transplant Recipients

Cited by 113 publications

References 36 publications

Immunogenicity and Safety of COVID-19 Vaccines in Patients Receiving Renal Replacement Therapy: A Systematic Review and Meta-Analysis

Immunogenicity and Safety of COVID-19 Vaccines in Patients Receiving Renal Replacement Therapy: A Systematic Review and Meta-Analysis

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

Cellular and humoral immune response to a third dose of BNT162b2 COVID-19 vaccine – a prospective observational study

Contact Info

Product

Resources

About