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      Humoral and cellular immune response to SARS-CoV-2 mRNA BNT162b2 vaccine in pediatric kidney transplant recipients compared with dialysis patients and healthy children

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          Abstract

          Background

          Compared with the general population, the immune response to COVID-19 mRNA vaccines is lower in adult kidney transplant recipients (KTRs). However, data is limited for pediatric KTRs. In this study, we aimed to assess humoral and cellular immune responses to the COVID-19 mRNA vaccine in pediatric KTRs.

          Methods

          This multicenter, prospective, case–control study included 63 KTRs (37 male, aged 12–21 years), 19 dialysis patients, and 19 controls. Humoral (anti-SARS-CoV2 IgG, neutralizing Ab (nAb)) and cellular (interferon-gamma release assay (IGRA)) immune responses were assessed at least one month after two doses of BNT162b2 mRNA vaccine.

          Results

          Among COVID-19 naïve KTRs ( n = 46), 76.1% tested positive for anti-SARS-CoV-2 IgG, 54.3% for nAb, and 63% for IGRA. Serum levels of anti-SARS-CoV-2 IgG and nAb activity were significantly lower in KTRs compared to dialysis and control groups ( p < 0.05 for all). Seropositivity in KTRs was independently associated with shorter transplant duration ( p = 0.005), and higher eGFR ( p = 0.007). IGRA titer was significantly lower than dialysis patients ( p = 0.009). Twenty (43.4%) KTRs were positive for all immune parameters. Only four of 11 seronegative KTRs were IGRA-positive. COVID-19 recovered KTRs had significantly higher anti-SARS-CoV-2 IgG and nAb activity levels than COVID-19 naïve KTRs ( p = 0.018 and p = 0.007, respectively).

          Conclusions

          The humoral and cellular immune responses to SARS-CoV-2 mRNA BNT162b2 vaccine are lower in pediatric KTRs compared to dialysis patients. Further prospective studies are required to demonstrate the clinical efficacy of the mRNA vaccine in KTRs.

          This prospective study was registered in ClinicalTrials.gov (NCT05465863, registered retrospectively at 20.07.2022).

          Graphical abstract

          A higher resolution version of the Graphical abstract is available as Supplementary information.

          Supplementary information

          The online version contains supplementary material available at 10.1007/s00467-022-05813-w.

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          Most cited references25

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          Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection

          David Khoury, Deborah Cromer, Arnold Reynaldi … (2021)
          Predictive models of immune protection from COVID-19 are urgently needed to identify correlates of protection to assist in the future deployment of vaccines. To address this, we analyzed the relationship between in vitro neutralization levels and the observed protection from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection using data from seven current vaccines and from convalescent cohorts. We estimated the neutralization level for 50% protection against detectable SARS-CoV-2 infection to be 20.2% of the mean convalescent level (95% confidence interval (CI) = 14.4-28.4%). The estimated neutralization level required for 50% protection from severe infection was significantly lower (3% of the mean convalescent level; 95% CI = 0.7-13%, P = 0.0004). Modeling of the decay of the neutralization titer over the first 250 d after immunization predicts that a significant loss in protection from SARS-CoV-2 infection will occur, although protection from severe disease should be largely retained. Neutralization titers against some SARS-CoV-2 variants of concern are reduced compared with the vaccine strain, and our model predicts the relationship between neutralization and efficacy against viral variants. Here, we show that neutralization level is highly predictive of immune protection, and provide an evidence-based model of SARS-CoV-2 immune protection that will assist in developing vaccine strategies to control the future trajectory of the pandemic.
          Article 0 comments Cited 1910 times – based on 0 reviews     Review now
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            Antibody Response to 2-Dose SARS-CoV-2 mRNA Vaccine Series in Solid Organ Transplant Recipients

            Brian J Boyarsky, William A Werbel, Robin K Avery … (2021)
            Article 0 comments Cited 525 times – based on 0 reviews     Review now
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              Results from the ERA-EDTA Registry indicate a high mortality due to COVID-19 in dialysis patients and kidney transplant recipients across Europe.

              Kitty Jager, Anneke Kramer, Nicholas Chesnaye … (2020)
              The aim of this study was to investigate 28-day mortality after COVID-19 diagnosis in the European kidney replacement therapy population. In addition, we determined the role of patient characteristics, treatment factors, and country on mortality risk using ERA-EDTA Registry data on patients receiving kidney replacement therapy in Europe between February 1, 2020 and April 30, 2020. Additional data on all patients with a diagnosis of COVID-19 were collected from seven European countries encompassing 4298 patients. COVID-19 attributable mortality was calculated using propensity-score matched historic controls and after 28 days of follow-up was 20.0% (95% confidence interval 18.7%-21.4%) in 3285 patients receiving dialysis, and 19.9% (17.5%-22.5%) in 1013 recipients of a transplant. We identified differences in COVID-19 mortality across countries, and an increased mortality risk in older patients receiving kidney replacement therapy and male patients receiving dialysis. In recipients of kidney transplants older than 75 years of age 44.3% (35.7%-53.9%) did not survive COVID-19. Mortality risk was 1.28 (1.02-1.60) times higher in transplant recipients compared with matched dialysis patients. Thus, the pandemic has had a substantial effect on mortality in patients receiving kidney replacement therapy; a highly vulnerable population due to underlying chronic kidney disease and high prevalence of multimorbidity.
              Article 0 comments Cited 239 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Ayse Agbas:
                ORCID: http://orcid.org/0000-0002-3658-8622
                ayse.agbas@iuc.edu.tr
                Journal
                Journal ID (nlm-ta): Pediatr Nephrol
                Journal ID (iso-abbrev): Pediatr Nephrol
                Title: Pediatric Nephrology (Berlin, Germany)
                Publisher: Springer Berlin Heidelberg (Berlin/Heidelberg )
                ISSN (Print): 0931-041X
                ISSN (Electronic): 1432-198X
                Publication date (Electronic): 2 December 2022
                Pages: 1-10
                Affiliations
                [1 ]GRID grid.506076.2, ISNI 0000 0004 1797 5496, Department of Pediatric Nephrology, , Cerrahpasa School of Medicine, IU-Cerrahpasa, ; Istanbul, Turkey
                [2 ]GRID grid.506076.2, ISNI 0000 0004 1797 5496, Department of Microbiology, , Cerrahpasa School of Medicine, IU-Cerrahpasa, ; Istanbul, Turkey
                [3 ]GRID grid.9601.e, ISNI 0000 0001 2166 6619, Department of Pediatric Nephrology, , Istanbul University School of Medicine, ; Istanbul, Turkey
                [4 ]GRID grid.9601.e, ISNI 0000 0001 2166 6619, Institute of Child Health, , Istanbul University, ; Istanbul, Turkey
                [5 ]GRID grid.16477.33, ISNI 0000 0001 0668 8422, Department of Pediatric Nephrology, , Marmara University School of Medicine, ; Istanbul, Turkey
                [6 ]GRID grid.411776.2, ISNI 0000 0004 0454 921X, Department of Pediatric Nephrology, , Medeniyet University School of Medicine, ; Istanbul, Turkey
                [7 ]GRID grid.459708.7, ISNI 0000 0004 7553 3311, Department of Pediatric Nephrology, , Istinye University School of Medicine, Liv Hospital, ; Istanbul, Turkey
                [8 ]GRID grid.506076.2, ISNI 0000 0004 1797 5496, Department of Pediatric Immunology and Allergy, , Cerrahpasa School of Medicine, IU-Cerrahpasa, ; Istanbul, Turkey
                [9 ]Department of Pediatric Nephrology, Memorial Hospital, Istanbul, Turkey
                Author information
                http://orcid.org/0000-0001-5504-3516
                http://orcid.org/0000-0002-0596-1551
                http://orcid.org/0000-0002-3658-8622
                http://orcid.org/0000-0003-3274-8024
                http://orcid.org/0000-0001-6805-5313
                http://orcid.org/0000-0002-3849-3280
                http://orcid.org/0000-0002-2424-6959
                http://orcid.org/0000-0002-6097-657X
                http://orcid.org/0000-0003-2891-2231
                http://orcid.org/0000-0002-5579-6339
                http://orcid.org/0000-0001-5821-3963
                http://orcid.org/0000-0002-0086-3936
                http://orcid.org/0000-0002-3420-9756
                http://orcid.org/0000-0002-3357-9237
                http://orcid.org/0000-0003-1072-3846
                http://orcid.org/0000-0002-3316-8032
                Article
                Publisher ID: 5813
                DOI: 10.1007/s00467-022-05813-w
                PMC ID: 9716124
                SO-VID: 3e464604-0c5f-4f65-bb05-f8a9e878bbf6
                Copyright © © The Author(s), under exclusive licence to International Pediatric Nephrology Association 2022, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
                License:

                This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

                History
                Date received : 11 July 2022
                Date revision received : 10 October 2022
                Date accepted : 31 October 2022
                Funding
                Funded by: Scientific Research Projects Coordination Unit of Istanbul University-Cerrahpasa
                Award ID: 35866
                Award Recipient :
                Categories
                Subject: Original Article

                ScienceOpen disciplines: Nephrology
                Keywords: mrna vaccine,bnt162b2,covid-19,immune response,anti-sars-cov-2 igg,igra,neutralizing antibody
                Data availability:
                ScienceOpen disciplines: Nephrology
                Keywords: mrna vaccine, bnt162b2, covid-19, immune response, anti-sars-cov-2 igg, igra, neutralizing antibody

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