Intravenous Immunoglobulins for Prevention of BKV Infection in Kidney Transplant Recipients According to BKV Genotype-specific Neutralizing Antibody Titers at the Day of Transplantation.

Abstract We aimed to evaluate the rate of anti–SARS-CoV-2 IgG seropositivity and investigated factors associated with seropositivity after the second SARS-CoV-2 mRNA vaccination in kidney transplant (KT) recipients. This retrospective study conducted between June 2021 and November 2021 included 106 KT recipients and 127 healthy controls who received the second dose of the BNT162b2 mRNA vaccine at least seven days before the measurement of antibody titers. The titers of immunoglobulin G (IgG) antibodies against the receptor-binding domain of SARS-CoV-2 spike (S) protein were determined. Seropositivity was defined as an anti–SARS-CoV-2 IgG level of ≥15 units/mL, which was considered as the presence of sufficient neutralizing antibodies. The median ages and the seroprevalence rates of the healthy controls and KT recipients were 68 and 56 years and 98% and 22%, respectively. Univariate logistic regression analysis revealed that age >53 years, rituximab use, mycophenolate mofetil use, and KT vintage <7 years were negatively associated with anti–SARS-CoV-2 IgG seropositivity in KT recipients. Humoral response after the second BNT162b2 mRNA vaccine was greatly hindered by immunosuppression therapy in KT recipients. Older age, rituximab use, mycophenolate mofetil use, and KT vintage may play key roles in seroconversion.

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SARS-CoV-2-specific Humoral and Cell-mediated Immune Responses after Immunization with Inactivated COVID-19 Vaccine in Kidney Transplant Recipients (CVIM 1 Study)

10.1101/2021.08.02.21261095 ◽

2021 ◽

Author(s):

Jackrapong Bruminhent ◽

Chavachol Sethaudom ◽

Pongsathon Chaumdee ◽

Sarinya Boongird ◽

Sasisopin Kiertiburanakul ◽

...

Keyword(s):

Kidney Transplant ◽

Organ Transplant ◽

Calcineurin Inhibitors ◽

Neutralizing Antibody ◽

Cell Mediated Immunity ◽

Solid Organ ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Cell Responses ◽

Clinical Trials Registry

Immunogenicity following inactivated SARS-CoV-2 vaccination among solid organ transplant recipients has not been assessed. Seventy-five patients (37 kidney transplant [KT] recipients and 38 non-transplant controls) received two doses, at 4-week intervals, of an inactivated whole-virus SARS-CoV-2 vaccine. SARS-CoV-2-specific humoral (HMI) and cell-mediated immunity (CMI) were measured before, 4 weeks post-first dose, and 2 weeks post-second dose. The median age of KT recipients was 50 years (IQR, 42 to 54) and 89% were receiving calcineurin inhibitors/mycophenolate/corticosteroid regimens. The median time since transplant was 4.5 years (IQR, 2 to 9.5). Among 35 KT patients, anti-RBD IgG titer after vaccination was not significantly different to baseline, but was significantly lower than in controls (7.8 [95%CI 0.2 to 15.5] vs 2,691 [95%CI 1,581 to 3,802], p<0.001) as well as the percentage of surrogate virus neutralizing antibody inhibition (2 [95% CI -1 to 6] vs 71 [95%CI 61 to 81], p<0.001). However, the mean of SARS-CoV-2 mixed peptides-specific T-cell responses measured by enzyme-linked immunospot assays was significantly increased compared with baseline (66 [95%CI 36 to 99] vs. 34 [95%CI 19 to 50] T-cells/10^6 PBMCs, p=0.02) and comparable to that in controls. Our findings revealed weak HMI and marginal CMI responses in fully vaccinated KT recipients receiving inactivated SARS-CoV-2 vaccine. (Thai Clinical Trials Registry, TCTR20210226002).

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Impaired immune response to SARS-CoV-2 vaccination in dialysis patients and in kidney transplant recipients

Kidney360 ◽

10.34067/kid.0003512021 ◽

2021 ◽

pp. 10.34067/KID.0003512021

Author(s):

Thilo Kolb ◽

Svenja Fischer ◽

Lisa Müller ◽

Nadine Lübke ◽

Jonas Hillebrandt ◽

...

Keyword(s):

Immune Responses ◽

Kidney Transplant ◽

Kidney Failure ◽

Neutralizing Antibodies ◽

Neutralizing Antibody ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Dialysis Patients ◽

Specific Antibodies ◽

Neutralization Capacity

Background: Kidney failure patients on dialysis or after renal transplantation have a high risk for severe COVID-19 infection and vaccination against SARS-CoV-2 is the only expedient prophylaxis. Generally, immune responses are attenuated in kidney failure patients, however, systematic analyses of immune responses to SARS-CoV-2 vaccination in dialysis patients and in kidney transplant recipients (KTR) are still missing. Methods: In this prospective multicentric cohort study, antibody responses COVID-19 mRNA vaccines (BNT162b2; Biontech/Pfizer or mRNA-1273; Moderna) were measured in 32 dialysis patients and in 28 KTRs. SARS-CoV-2-specific antibodies and neutralization capacity were evaluated and compared to controls (n=78) in a similar age-range. Results: After the first vaccination, SARS-CoV-2-specific antibodies were nearly undetectable in kidney failure patients. After the second vaccination, 93% of the controls and 88% of dialysis patients but only 37% of KTRs developed SARS-CoV-2-specific IgG above cut-off. Moreover, mean IgG levels were significantly lower in KTRs (54±93 BAU/ml) compared to dialysis patients (503±481 BAU/ml, p<0.01). Both KTRs as well as dialysis patients had significantly lower IgG levels compared to controls (1992±2485 BAU/ml; p<0.001 and p<0.01). Importantly, compared to controls, neutralizing antibody titers were significantly lower in KTRs and dialysis patients. After the second vaccination, 76% of KTRs did not show any neutralization capacity against SARS-CoV-2 suggesting impaired seroprotection. Conclusions: Kidney failure patients show a significantly weaker antibody response compared to controls. Most strikingly, only one out four KTRs developed neutralizing antibodies against SARS-CoV-2 after two doses of vaccine. These data suggest that vaccination strategies need modification in immune transplant and dialysis patients.

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Six-Month Follow-Up after Vaccination with BNT162b2: SARS-CoV-2 Antigen-Specific Cellular and Humoral Immune Responses in Hemodialysis Patients and Kidney Transplant Recipients

Pathogens ◽

10.3390/pathogens11010067 ◽

2022 ◽

Vol 11 (1) ◽

pp. 67

Author(s):

Simone Cosima Boedecker-Lips ◽

Anja Lautem ◽

Stefan Runkel ◽

Pascal Klimpke ◽

Daniel Kraus ◽

...

Keyword(s):

Immune Responses ◽

Kidney Transplant ◽

Cell Response ◽

Cellular Response ◽

Chronically Ill ◽

Response Rates ◽

Hemodialysis Patients ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Antibody Titers

Hemodialysis patients (HDP) and kidney transplant recipients (KTR) have a high risk of infection with SARS-CoV-2 with poor clinical outcomes. Because of this, vaccination of these groups of patients against SARS-CoV-2 is particularly important. However, immune responses may be impaired in immunosuppressed and chronically ill patients. Here, our aim was to compare the efficacy of an mRNA-based vaccine in HDP, KTR, and healthy subjects. Design: In this prospective observational cohort study, the humoral and cellular response of prevalent 192 HDP, 50 KTR, and 28 healthy controls (HC) was assessed 1, 2, and 6 months after the first immunization with the BNT162b2 mRNA vaccine. Results: After 6 months, 97.5% of HDP, 37.9% of KTR, and 100% of HC had an antibody response. Median antibody levels were 1539.7 (±3355.8), 178.5 (±369.5), and 2657.8 (±2965.8) AU/mL in HDP, KTR, and HC, respectively (p ≤ 0.05). A SARS-CoV-2 antigen-specific cell response to vaccination was found in 68.8% of HDP, 64.5% of KTR, and 90% of HC. Conclusion: The humoral response rates to mRNA-based vaccination of HDPs are comparable to HCs, but antibody titers are lower. Furthermore, HDPs have weaker T-cell response to vaccination than HCs. KTRs have very low humoral and antigen-specific cellular response rates and antibody titers, which requires other vaccination strategies in addition to booster vaccination.

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Humoral Response after SARS-Cov-2 mRNA Vaccine in a Cohort of Hemodialysis Patients and Kidney Transplant Recipients

Journal of the American Society of Nephrology ◽

10.1681/asn.2021040490 ◽

2021 ◽

pp. ASN.2021040490

Author(s):

Clément Danthu ◽

Sébastien Hantz ◽

Arthur Dahlem ◽

Marion Duval ◽

Bacary Ba ◽

...

Keyword(s):

Kidney Transplant ◽

Humoral Response ◽

Hemodialysis Patients ◽

Hepatitis B Vaccination ◽

Serological Response ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Medical File ◽

Hbv Vaccine ◽

Antibody Titers

Background Kidney transplant recipients and patients receiving hemodialysis are immunocompromised populations that are prioritized for COVID-19 vaccination but were excluded from clinical trials of SARS-CoV-2 mRNA vaccines. Antibody titers and rates of seroconversion following vaccination are lower among patients with chronic kidney disease and those taking immunosuppressants compared with controls. Data are lacking regarding their humoral response to vaccination to prevent COVID-19. Methods This investigation of early serological response after COVID-19 vaccination with the Pfizer/BioNTech (BNT162b2) mRNA vaccine included 78 patients undergoing hemodialysis, 74 kidney transplant recipients, and 7 healthy controls. We recorded data from the medical file for various clinical parameters, including response to hepatitis B vaccination, and measured antibody titers against SARS-CoV-2 at 0, 14, 28, 36 and 58 days after the first injection. Results In controls, we detected antibodies at a positive level (>13 arbitrary units per milliliter [AU/ml]) at day 14 postinjection, which increased progressively to peak at day 36 (1082 AU/ml; interquartile range [IQR], 735.0-1662.0]). Patients undergoing hemodialysis had lower titers that peaked at day 58 (276 AU/ml [IQR, 83.4-526.0]. We detected a positive antibody level in only three transplant recipients at day 36. In hemodialysis patients, those younger than 75 years had a higher antibody response versus those older than 75 years and serum albumin and Kt/V were positively correlated with serological response (P< 0.043 and P<0.019, respectively); nonresponders to HBV vaccine had the lowest anti-SARS-CoV-2 antibody titers. Conclusions Our results suggest that the postvaccination humoral response is strongly inhibited by immunosuppressant therapy in kidney transplant recipients and is reduced by the uremic condition in patients undergoing hemodialysis.

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A fourth dose of the mRNA-1273 SARS-CoV-2 vaccine improves serum neutralization against the delta variant in kidney transplant recipients

10.1101/2021.11.25.21266704 ◽

2021 ◽

Author(s):

Ilies Benotmane ◽

Timothée Bruel ◽

Delphine Planas ◽

Samira Fafi-Kremer ◽

Olivier Schwartz ◽

...

Keyword(s):

Antibody Response ◽

Kidney Transplant ◽

Neutralizing Antibody ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Serum Neutralization ◽

Before And After ◽

Fourth Dose ◽

Alpha Variant ◽

Kinetics Of

In immunocompetent subjects, the effectiveness of SARS-CoV-2 vaccines against the delta variant appears three-to five-fold lower than that observed against the alpha variant. Additionally, three doses of SARS-CoV-2 mRNA-based vaccines might be unable to elicit a sufficient immune response against any variant in immunocompromised kidney transplant recipients. This study describes the kinetics of the neutralizing antibody (NAbs) response against the delta strain before and after a fourth dose of a mRNA vaccine in 67 kidney transplant recipients who had experienced a weak antibody response after three doses. While only 16% of patients harbored NAbs against the delta strain prior to the fourth injection – this percentage raised to 66% afterwards. We also found that, after the fourth dose, the NAbs titer increased significantly (p=0.0001) from <7.5 (IQR : <7.5 –15.1) to 47.1 (IQR <7.5–284.2). Collectively, our data indicate that a fourth dose of the mRNA-1273 vaccine in kidney transplant recipients with a weak antibody response after three previous doses improves serum neutralization against the delta variant.

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mRNA-1273 vaccine (Moderna): a better option than BNT162b2 (Pfizer) in kidney transplant recipients and dialysis patients?

10.1101/2021.09.15.21263320 ◽

2021 ◽

Author(s):

Veerle P.W.M. Wijtvliet ◽

Kevin K. Arien ◽

Steven Abrams ◽

Marie M. Couttenye ◽

Fabienne Mestrez ◽

...

Keyword(s):

Immune Response ◽

Kidney Transplant ◽

Humoral Immune Response ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Dialysis Patients ◽

Humoral Immune ◽

Antibody Titers

In this study of the humoral immune response after the first dose of SARS-CoV-2 mRNA vaccine, low seroconversion rates were noted in both kidney transplant recipients and dialysis patients. However, vaccination with the mRNA-1273 vaccine (Moderna) resulted in both higher seroconversion rates and mean antibody titers compared to BNT162b2 (Pfizer).

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