Reduced humoral response to mRNA SARS‐Cov‐2 BNT162b2 vaccine in kidney transplant recipients without prior exposure to the virus. No cause for alarm

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 to a 13-valent pneumococcal conjugate vaccine in kidney transplant recipients

Vaccine ◽

10.1016/j.vaccine.2020.02.088 ◽

2020 ◽

Vol 38 (17) ◽

pp. 3339-3350 ◽

Cited By ~ 1

Author(s):

Simon Oesterreich ◽

Monika Lindemann ◽

David Goldblatt ◽

Peter A. Horn ◽

Benjamin Wilde ◽

...

Keyword(s):

Kidney Transplant ◽

Conjugate Vaccine ◽

Pneumococcal Conjugate Vaccine ◽

Humoral Response ◽

Transplant Recipients ◽

Kidney Transplant Recipients

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Real-world Effectiveness of 2-dose SARS-CoV-2 Vaccination in Kidney Transplant Recipients

10.1101/2021.09.21.21263457 ◽

2021 ◽

Author(s):

Caitriona M. McEvoy ◽

Anna Lee ◽

Paraish S. Misra ◽

Gerald Lebovic ◽

Ron Wald ◽

...

Keyword(s):

Cohort Study ◽

Kidney Transplant ◽

Real World ◽

Humoral Response ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

The Real ◽

Transplant Program ◽

The Impact

The humoral response to two doses of SARS-CoV-2 (Covid-19) vaccine among transplant recipients is inferior to immunocompetent individuals. Data on the real-world effectiveness of vaccination in kidney transplant recipients [KTRs] are lacking. We performed a cohort study to investigate the impact of vaccination on Covid-19 infection and outcomes in our kidney transplant program.

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The 5-months impact of tozinameran (BNT162b2) mRNA vaccine on kidney transplant and chronic dialysis patients

10.1101/2021.06.12.21258813 ◽

2021 ◽

Author(s):

Iddo Z. Ben-Dov ◽

Yonatan Oster ◽

Keren Tzukert ◽

Talia Alster ◽

Raneem Bader ◽

...

Keyword(s):

Antibody Response ◽

Kidney Transplant ◽

Humoral Response ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Dialysis Patients ◽

Transplant Patients ◽

Vitamin D Levels ◽

Kidney Transplant Patients ◽

Inhibitor Drug

Background: Determining the humoral immunogenicity of tozinameran (BNT162b2) vaccine in patients requiring chronic renal replacement therapy, and its impact on COVID-19 morbidity several months after vaccination, will guide risk assessment and subsequent changes in vaccination policy. Methods: In a prospective post-vaccination cohort study with up to 5 months follow-up we studied outpatient dialysis and kidney transplant patients and respective healthcare teams. Outcomes were anti S1/S2 antibody response to vaccine or infection and infection rate during followup. Results: 175 dialysis patients (40% women, 65+/-15 years), 252 kidney transplant patients (33% women, 54+/-14 years) and 71 controls (65% women, 44+/-14 years) were followed. Three months or longer after vaccination we detected anti S1/S2 IgG antibodies in 80% of dialysis patients, 44% of transplant recipients and 100% of controls, whereas respective rates after infection were 94%, 75% and 100%. Predictors of non-response were age, diabetes, history of cancer, lower lymphocyte count and lower vitamin-D levels. Factors associated with lower titers in dialysis patients were modality (hemodialysis vs peritoneal) and serum ferritin levels. In transplant patients, hypertension and higher calcineurin or mTOR inhibitor drug levels were linked with diminished antibody response. Vaccination associated with fewer subsequent infections (HR=0.23, p<0.05). Moreover, higher antibody titers associated with fewer events, HR 0.41 for each unit increased in log10titer (p<0.05). Conclusions: Dialysis patients, and more so kidney transplant recipients, mounted delayed and reduced antibody response to COVID-19 mRNA vaccination, and lesser humoral response associated with more infections. Measures to identify and protect non-responsive patients are urgently required.

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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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Cellular and humoral response after mRNA‐1273 SARS‐CoV‐2 vaccine in kidney transplant recipients

American Journal of Transplantation ◽

10.1111/ajt.16701 ◽

2021 ◽

Author(s):

David Cucchiari ◽

Natalia Egri ◽

Marta Bodro ◽

Sabina Herrera ◽

Jimena Del Risco‐Zevallos ◽

...

Keyword(s):

Kidney Transplant ◽

Humoral Response ◽

Transplant Recipients ◽

Kidney Transplant Recipients

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