Risk of strong antibody decline in dialysis and transplant patients after SARS-CoV-2mRNA vaccination: Six months data from the observational Dia-Vacc study

Stumpf, Julian; Schwöbel, Jörg; Lindner, Tom H.; Anders, Leona; Siepmann, Torsten; Karger, Claudia; Hüther, Jan; Martin, Heike; Müller, Petra; Faulhaber-Walter, Robert; Langer, Torsten; Schirutschke, Holger; Stehr, Thomas; Meistring, Frank; Pietzonka, Annegret; Anding-Rost, Kirsten; Escher, Katja; Pistrosch, Frank; Schewe, J.-C.; Seidel, Harald; Barnett, Kerstin; Pluntke, Thilo; Cerny, Simon; Paliege, Alexander; Bast, Ingolf; Steglich, Anne; Gembardt, Florian; Kessel, Friederike; Kröger, Hannah; Arndt, Patrick; Sradnick, Jan; Frank, Kerstin; Klimová, Anna; Mauer, René; Grählert, Xina; Tonn, Torsten; Hugo, Christian

doi:10.1016/j.lanepe.2022.100371

Cited by 19 publications

(13 citation statements)

References 23 publications

(35 reference statements)

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“…However, it has been shown that the immune response to SARS-CoV-2 vaccination in immunocompromised persons is lower than in controls (2-5), and solid-organ transplant (SOT) recipients have impaired immune response to SARS-CoV-2 vaccination even after the third or fourth vaccine doses (3,(6)(7)(8)(9)(10)(11). Previous studies that investigated the immune response to SARS-CoV-2 vaccination in SOT recipients have focused on humoral immune responses, mainly on anti-SARS-CoV-2 IgG antibodies, with longitudinal follow-ups shorter than six months after first or second vaccine doses (12)(13)(14)(15)(16)(17). In a previous study on SOT recipients from Denmark, anti-SARS-CoV-2 IgG antibodies were measured nine months after the second vaccine dose (18).…”

Section: Introductionmentioning

confidence: 99%

Humoral and T-cell response 12 months after the first BNT162b2 vaccination in solid organ transplant recipients and controls: Kinetics, associated factors, and role of SARS-CoV-2 infection

et al. 2023

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IntroductionWe investigated humoral and T-cell responses within 12 months after first BNT162b2 vaccine in solid organ transplant (SOT) recipients and controls who had received at least three vaccine doses. Furthermore, we compared the immune response in participants with and without previous SARS-CoV-2 infection.MethodsWe included adult liver, lung, and kidney transplant recipients, and controls were selected from a parallel cohort of healthcare workers.ResultsAt 12th-month, the IgG geometric mean concentrations (GMCs) (P<0.001), IgA GMCs (P=0.003), and median IFN-γ (P<0.001) were lower in SOT recipients than in controls. However, in SOT recipients and controls with previous infection, the neutralizing index was 99%, and the IgG, and IgA responses were comparable. After adjustment, female-sex (aOR: 3.6, P<0.009), kidney (aOR: 7.0, P= 0.008) or lung transplantation (aOR: 7.5, P= 0.014), and use of mycophenolate (aOR: 5.2, P=0.03) were associated with low IgG non response. Age (OR:1.4, P=0.038), time from transplantation to first vaccine (OR: 0.45, P<0.035), and previous SARS-CoV-2 infection (OR: 0.14, P<0.001), were associated with low IgA non response. Diabetes (OR:2.4, P=0.044) was associated with T-cell non response.ConclusionIn conclusion, humoral and T-cell responses were inferior in SOT recipients without previous SARS-CoV-2 infection but comparable to controls in SOT recipients with previous infection.

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Section: Introductionmentioning

confidence: 99%

Humoral and T-cell response 12 months after the first BNT162b2 vaccination in solid organ transplant recipients and controls: Kinetics, associated factors, and role of SARS-CoV-2 infection

et al. 2023

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“…Hereby, studies including our Dia-Vacc study identified the anti-metabolite MMF/MPA (besides belatacept) as the critical immunosuppressive drug type being associated with seroconversion failure at 2 months after SARS-CoV-2 vaccination in KTR ( 1 – 3 ). During 6 months of follow-up investigations, seroconverted KTR [compared to medical personnel (MP)] were at risk for a strong decline in IgG and RBD-IgG antibodies but neither IgA antibodies nor cellular immunity ( 4 ). Hereby, antibody titers of KTR peaked at a lower level, and pronounced antibody decline was mixed with an increasing IgG or RBD-IgG response in at least 15% of patients.…”

Section: Introductionmentioning

confidence: 99%

MMF/MPA Is the Main Mediator of a Delayed Humoral Response With Reduced Antibody Decline in Kidney Transplant Recipients After SARS-CoV-2 mRNA Vaccination

Stumpf

Siepmann

Schwöbel³

et al. 2022

Front. Med.

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Kidney transplant recipients (KTR) show significantly lower seroconversion rates after SARS-CoV-2 mRNA vaccination compared to dialysis patients (DP). Mycophenolate mofetil or mycophenolic acid (MMF/MPA) in particular has been identified as a risk factor for seroconversion failure. While the majority of all KTR worldwide receive MMF/MPA for immunosuppressive therapy, its impact on antibody decline in seroconverted KTR still remains unclear. In an observational study (NCT04799808), we investigated whether 132 seroconverted KTR (anti-spike S1 IgG or IgA positive after 2 vaccinations) show a more rapid antibody decline with MMF/MPA than those without this medication. A total of 2 months after mRNA vaccination, average anti-spike S1 IgG levels of KTR with MMF/MPA were lower than without (p = 0.001), while no differences between these two groups were observed after 6 months (p = 0.366). Similar results were obtained for anti-RBD IgG antibodies (T2 p = 0.003 and T3 p = 0.135). The probability of severe IgG decline with MMF/MPA was three times lower than without (p = 0.003, OR 0.236, 95% CI 0.091–0.609). In the multivariate analysis, neither immunosuppressants, such as calcineurin inhibitors, mTOR inhibitors (mTOR-I; mechanistic target of rapamycin), glucocorticoids, nor vaccine type, sex, or age showed a significant influence on IgG titer decline between 2 and 6 months. For the decision on additional booster vaccinations, we consider immunosurveillance to be needed as an integral part of renal transplant follow-up after SARS-CoV-2 mRNA vaccination. Not only the lack of seroconversion but also the peak and titer decline of the specific IgG and RBD IgG antibody formation after two mRNA vaccinations is significantly influenced by MMF/MPA.

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“…In patients on PD, SARS-CoV-2 vaccination has demonstrated to be safe and to promote early and strong seroconversion at least with the initial schedule (i.e., two doses of mRNA-based vaccines [BNT162b2, mRNA-1273] or ChAdOx1-S or one dose of Ad26.COV.2) [ 6 , 11 ]. However, anti-spike antibody titers in PD decrease over time, as is the case for other RRT patients, potentially leading to suboptimal protection against SARS-CoV-2 [ 12 , 13 ]. In this regard, a booster (or third) dose was considered early for these vulnerable patients.…”

Section: Introductionmentioning

confidence: 99%

Long-Term Dynamic Humoral Response to SARS-CoV-2 mRNA Vaccines in Patients on Peritoneal Dialysis

Quiroga

Soler²,

Ortíz³

et al. 2022

Vaccines

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Introduction. Patients on peritoneal dialysis (PD) present an impaired humoral response against SARS-CoV-2, at least after the initial vaccination and booster dose. Until now, the effect of a fourth dose has not been established. The aim of the present study is to evaluate the long-term dynamics of the humoral response of PD patients to multiple doses of SARS-CoV-2 vaccines, focusing on the effect of the fourth dose. Methods. This is an analysis of the prospective and multicentric SENCOVAC study. We included patients on PD without additional immunosuppression that had received at least 3 SARS-CoV-2 mRNA vaccine doses. We evaluated anti-spike antibody titers after the initial vaccination, third and fourth doses, using prespecified fixed assessments (i.e., baseline, 28 days, 3, 6, and 12 months after completing the initial vaccine schedule). Breakthrough infections were also collected. Results. We included 164 patients on PD (69% males, 62 ± 13 years old). In patients who had received only two doses, the rates of positive humoral response progressively decreased from 96% at 28 days to 80% at 6 months, as did with anti-spike antibody titers. At 6 months, 102 (62%) patients had received the third vaccine dose. Patients with the third dose had higher rates of positive humoral response (p = 0.01) and higher anti-spike antibody titers (p < 0.001) at 6 months than those with only 2 doses. At 12 months, the whole cohort had received 3 vaccine doses, and 44 (27%) patients had an additional fourth dose. The fourth dose was not associated to higher rates of positive humoral response (100 vs. 97%, p = 0.466) or to statistically significant differences in anti-spike antibody titers as compared to three doses (p = 0.371) at 12 months. Prior antibody titers were the only predictor for subsequent higher anti-spike antibody titer (B 0.53 [95%CI 0.27–0.78], p < 0.001). The 2 (1.2%) patients that developed COVID-19 during follow-up had mild disease. Conclusions. PD presents an acceptable humoral response with three doses of SARS-CoV-2 vaccines that improve the progressive loss of anti-spike antibody titers following two vaccine doses.

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Risk of strong antibody decline in dialysis and transplant patients after SARS-CoV-2mRNA vaccination: Six months data from the observational Dia-Vacc study

Cited by 19 publications

References 23 publications

Humoral and T-cell response 12 months after the first BNT162b2 vaccination in solid organ transplant recipients and controls: Kinetics, associated factors, and role of SARS-CoV-2 infection

Humoral and T-cell response 12 months after the first BNT162b2 vaccination in solid organ transplant recipients and controls: Kinetics, associated factors, and role of SARS-CoV-2 infection

MMF/MPA Is the Main Mediator of a Delayed Humoral Response With Reduced Antibody Decline in Kidney Transplant Recipients After SARS-CoV-2 mRNA Vaccination

Long-Term Dynamic Humoral Response to SARS-CoV-2 mRNA Vaccines in Patients on Peritoneal Dialysis

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