Seroprevalence of SARS-CoV-2 IgG Antibodies After the Second BNT162b2 mRNA Vaccine in Japanese Kidney Transplant Recipients

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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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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Mycophenolate mofetil, together with cyclosporin A, prevents anti-OKT3 antibody response in kidney transplant recipients.

Journal of the American Society of Nephrology ◽

10.1681/asn.v981521 ◽

1998 ◽

Vol 9 (8) ◽

pp. 1521-1525

Author(s):

N Broeders ◽

K M Wissing ◽

A Crusiaux ◽

P Kinnaert ◽

P Vereerstraeten ◽

...

Keyword(s):

Monoclonal Antibody ◽

Mycophenolate Mofetil ◽

Kidney Transplant ◽

Humoral Response ◽

Enzyme Linked Immunosorbent Assay ◽

Blood Levels ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Serum Samples ◽

The Impact

OKT3 monoclonal antibody, a murine IgG2a monoclonal antibody targeting the T cell CD3 antigen, elicits a neutralizing humoral response in 20 to 50% of kidney transplant recipients when the concomitant immunosuppression consists of CsA-Sandimmun (SAND) and azathioprine (AZA). In the present study, we investigated the impact of the newer agents, CsA-Neoral (NEO) and mycophenolate mofetil (MMF) on OKT3 sensitization. Sixty-two consecutive kidney transplant recipients received prophylactic OKT3 (5 mg/d) from days 0 to 13, together with steroids. Concomitant immunosuppression consisted of either AZA + SAND (n=20), AZA + NEO (n=31), or MMF + NEO (n=11). The following doses were used: AZA, 2 mg/kg per d from days 0 to 13, then 1 mg/kg per d; MMF, 2 g/d starting on day 1; and CsA, either SAND or NEO, 6 mg/kg per d from day 6. At least two serum samples per month were available during the initial 3 mo for each patient. IgG anti-OKT3 antibodies were first evaluated by enzyme-linked immunosorbent assay. Patients were considered sensitized if their serum scored positive at a dilution > or = 1/1000. Peak titers of IgG anti-OKT3 antibodies and the incidence of patients harboring neutralizing anti-idiotypic antibodies were also determined. A first reduction in OKT3 sensitization was seen in patients receiving Neoral instead of Sandimmun (AZA + SAND: 10 of 20 [50%] patients sensitized versus 6 of 31 [19%] in the AZA + NEO group; P=0.03). This was probably related to the achievement of higher mean CsA trough blood levels in the NEO group during the first month (253+/-44 versus 186+/-49 ng/ml in SAND patients). Peak antibody titers and the proportion of patients with anti-idiotypic antibodies were similar in the AZA + SAND and AZA + NEO groups. A further reduction in the sensitization rate was observed with the replacement of AZA by MMF (MMF + NEO: 0% sensitized patients; P=0.0013). It is concluded that the combination of CsA-Neoral and MMF efficiently prevents sensitization against OKT3.

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Predictors of Humoral Response to mRNA COVID19 Vaccines in Kidney Transplant Recipients: A Longitudinal Study—The COViNEPH Project

Vaccines ◽

10.3390/vaccines9101165 ◽

2021 ◽

Vol 9 (10) ◽

pp. 1165

Author(s):

Alicja Dębska-Ślizień ◽

Zuzanna Ślizień ◽

Marta Muchlado ◽

Alicja Kubanek ◽

Magdalena Piotrowska ◽

...

Keyword(s):

Kidney Transplant ◽

Seroconversion Rate ◽

Booster Vaccination ◽

Humoral Response ◽

Transplant Recipients ◽

Igg Antibodies ◽

Kidney Transplant Recipients ◽

Younger Age ◽

Subgroup Analyses ◽

Immunosuppressive Protocol

Background: The efficacy of SARS-CoV-2 vaccination among kidney transplant recipients (KTR) is low. The main goal of this study was to analyze factors that may influence the humoral response to vaccination. Methods: We analyzed the titer magnitude of IgG antibodies directed against spike (S)-SARS-CoV-2 antigen after the second dose of the mRNA vaccine in 142 infection naïve KTR (83 men, i.e., 58.4%) with a median age (IQR) of 54 (41–63), and 36 respective controls without chronic kidney disease. mRNA-1273 or BNT162b2 were applied in 26% and 74% of KTR, respectively. Results: S-specific immune response (seroconversion) was seen in 73 (51.41%) of KTR, and in all controls 36 (100%). Independent predictors of no response were elder age, shorter transplantation vintage, and a more than two-drug immunosuppressive protocol. In subgroup analyses, the seroconversion rate was highest among KTR without MMF/MPS treatment (70%), treated with no more than two immunosuppressants (69.2%), treated without corticosteroid (66.7%), younger patients aged <54 years (63.2%), and those vaccinated with the mRNA-1273 vaccine (62.16%). The independent predictors of higher S-antibody titer among responders were younger age, treatment with no more than two immunosuppressants, and the mRNA-1273 vaccination. Conclusions: Our study confirmed a low rate of seroconversion after vaccination with the mRNA vaccine in KTR. The major modifiable determinants of humoral response were the composition of the immunosuppressive protocol, as well as the type of vaccine. The latter could be taken into consideration when initial vaccination as well as booster vaccination is considered in KTR.

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Neutralization of SARS-CoV-2 Variants of Concern in Kidney Transplant Recipients after Standard COVID-19 Vaccination

Clinical Journal of the American Society of Nephrology ◽

10.2215/cjn.11820921 ◽

2021 ◽

pp. CJN.11820921

Author(s):

Louise Benning ◽

Christian Morath ◽

Marie Bartenschlager ◽

Christian Nusshag ◽

Florian Kälble ◽

...

Keyword(s):

Immune Response ◽

Kidney Transplant ◽

Neutralizing Antibodies ◽

Immune Escape ◽

Interquartile Range ◽

Healthy Controls ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Clinical Trial Registry ◽

Median Serum

Background and objectivesAntibody response after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination is impaired in kidney transplant recipients. Emerging variants, such as B.1.617.2 (δ), are of particular concern because of their higher transmissibility and partial immune escape. Little is known about protection against these variants in immunocompromised patients.Design, setting, participants, & measurementsIn this prospective two-center study, antispike 1 IgG and surrogate neutralizing antibodies were measured in 173 kidney transplant recipients and 166 healthy controls with different vaccination schedules. In addition, different SARS-CoV-2 epitope antibodies from 135 vaccinated kidney transplant recipients were compared with antibodies in 25 matched healthy controls after second vaccination. In 36 kidney transplant recipients with seroconversion, neutralization against B.1.1.7 (α), B.1.351 (β), and B.1.617.2 (δ) was determined on VeroE6 cells and compared with neutralization in 25 healthy controls.ResultsKidney transplant recipients had significantly lower seroconversion rates compared with healthy controls. After the second vaccination, antispike 1, antireceptor-binding domain, and surrogate neutralizing antibodies were detectable in 30%, 27%, and 24% of kidney transplant recipients, respectively. This compares with 100%, 96%, and 100% in healthy controls, respectively (P<0.001). Neutralization against B.1.1.7 was detectable in all kidney transplant recipients with seroconversion, with a median serum dilution that reduces infection of cells by 50% of 80 (interquartile range, 80–320). In contrast, only 23 of 36 (64%) and 24 of 36 (67%) kidney transplant recipients showed neutralization against B.1.351 and B.1.617.2, respectively, with median serum dilutions that reduce infection of cells by 50% of 20 (interquartile range, 0–40) and 20 (interquartile range, 0–40), respectively. Neutralization against different variants was significantly higher in healthy controls (P<0.001), with all patients showing neutralization against all tested variants.ConclusionsSeroconverted kidney transplant recipients show impaired neutralization against emerging variants of concern after standard two-dose vaccination.Clinical Trial registry name and registration number:Observational study to assess the SARS-CoV-2 specific immune response in kidney transplant recipients (COVID-19 related immune response), DRKS00024668

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Boosting Humoral Immunity from mRNA COVID-19 Vaccines in Kidney Transplant Recipients

Vaccines ◽

10.3390/vaccines10010056 ◽

2021 ◽

Vol 10 (1) ◽

pp. 56

Author(s):

Leszek Tylicki ◽

Alicja Dębska-Ślizień ◽

Marta Muchlado ◽

Zuzanna Ślizień ◽

Justyna Gołębiewska ◽

...

Keyword(s):

Kidney Transplant ◽

Secondary Analysis ◽

Humoral Response ◽

Primary Vaccination ◽

Transplant Recipients ◽

Igg Antibodies ◽

Kidney Transplant Recipients ◽

Serious Adverse Events ◽

The Third ◽

Longitudinal Observational Study

Introduction: The immune response to the primary (two-dose) series of mRNA COVID-19 vaccines in kidney transplant recipients (KTRs) is very weak. We conducted a longitudinal observational study to compare the humoral response to a third, additional primary dose of mRNA vaccines between infection-naïve (IN-KTRs) and previously infected KTRs (PI-KTRs). Methods: We measured the levels of anti-spike (anti-s) IgG antibodies before and 14–21 days after the third dose and, in the secondary analysis, we compared the antibody response to BNT162b2 versus mRNA-1273. The reactogenicity assessment included solicited local and systemic reactions. Results: A total of 112 KTRs were enrolled, including 83 IN-KTR and 29 PI-KTR, among whom seroconversion in anti-s antibodies after the primary two-dose vaccination was achieved in 45.78% and 100% of cases, respectively. After three months, a waning antibodies titer by 67.4% (IN-KTR) and 7.5% (PI-KTR) was observed. After the third dose of the mRNA vaccine, 71.08% (59/83) of IN-KTR and 96.5% (28/29) of PI-KTR samples were seroconverted with a median anti-s titer of 468.0 (195.0–1620.0) BAU/mL and 1629.0 (1205–1815) BAU/mL, respectively. Of those IN-KTR in whom the primary vaccination failed, 46.67% (21/45) of patients achieved seroconversion after the third dose. No serious adverse events after the third dose were reported. In strata analyses, after the third dose, 66% (40/60) of patients vaccinated with BNT162b2 and 82.6% (19/23) of patients vaccinated with mRNA-1273 seroconverted with a median anti-s titer of 384.5 (144–837) BAU/mL and 1620 (671–2040) BAU/mL, respectively. Conclusions: The use of a third dose of mRNA vaccine may be of benefit for KTR, especially for those in whom the primary vaccination failed. Vaccines with a higher dose of mRNA and a longer interval between doses of the primary vaccination, such as mRNA-1273, seem to be the preparations of choice in immunocompromised individuals.

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