B and T Cell Responses after a Third Dose of SARS-CoV-2 Vaccine in Kidney Transplant Recipients
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Abstract
Protection of solid organ transplant recipients against SARS-CoV-2 by vaccination remains an unmet need, given the low immunogenicity of available vaccines in the presence of immunosuppression. Administration of a third dose to 25 kidney transplant recipients (KTR) resulted in seroconversion in 36% of patients, associated with significant quantitative and functional changes within the spike-antigen–specific B cell and CD4 + T-helper cell compartment. Our data support the need for individual humoral monitoring of immunosuppressed individuals after vaccination and continued efforts to adapt vaccination protocols for this at-risk group.
Background
Accumulating evidence sugges ts solid organ transplant recipients, as opposed to the general population, show strongly impaired responsiveness toward standard SARS-CoV-2 mRNA-based vaccination, demanding alternative strategies for protectio n o f this vulnerable group.
Methods
In line with recent recommendations, a third dose of either heterologous ChAdOx1 (AstraZeneca) or homologous BNT162b2 (BioNTech) was administered to 25 kidney transplant recipients (KTR) without humoral response after two doses of BNT162b2, followed by analysis of serological responses and vaccine-specific B- and T-cell immunity.
Results
Nine out of 25 (36%) KTR under standard immunosuppressive treatment seroconverted until day 27 after the third vaccination, whereas one patient developed severe COVID-19 infection immediately after vaccination. Cellular analysis 7 days after the third dose showed significantly elevated frequencies of viral spike-protein receptor-binding domain-specific B cells in humor al responders as compared with nonresponders. Likewise, portions of spike-reactive CD4 + T helper cells were significantly elevated in patients who were seroconverting. Furthermore, overall frequencies of IL-2 + , IL-4 + , and polyfunctional CD4 + T cells significantly increased after the third dose, whereas memory/effector differentiation remained unaffected.
Conclusions
Our data suggest a fraction of transplant recipients benefit from triple vaccination, where seroconversion is associated with quantitative and qualitative changes of cellular immunity. At the same time, the study highlights that modified vaccination approaches for immunosuppressed patients remain an urgent medical need.
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SciScore for 10.1101/2021.08.12.21261966: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics Consent: All participants gave written informed consent for sample collection according to the approval of the ethics committees of the Charité-Universitätsmedizin Berlin (EA2/010/21, EA4/188/20), of the county of Saxony-Anhalt (EA7/21) and the University of Greifswald (BB019/21).
IRB: All participants gave written informed consent for sample collection according to the approval of the ethics committees of the Charité-Universitätsmedizin Berlin (EA2/010/21, EA4/188/20), of the county of Saxony-Anhalt (EA7/21) and the University of Greifswald (BB019/21).Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Table 2: Resources
… SciScore for 10.1101/2021.08.12.21261966: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics Consent: All participants gave written informed consent for sample collection according to the approval of the ethics committees of the Charité-Universitätsmedizin Berlin (EA2/010/21, EA4/188/20), of the county of Saxony-Anhalt (EA7/21) and the University of Greifswald (BB019/21).
IRB: All participants gave written informed consent for sample collection according to the approval of the ethics committees of the Charité-Universitätsmedizin Berlin (EA2/010/21, EA4/188/20), of the county of Saxony-Anhalt (EA7/21) and the University of Greifswald (BB019/21).Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Table 2: Resources
Antibodies Sentences Resources For detection of surface molecules, antibodies against CD3 (SK7, Biolegend, Carlsbad, CA, USA), CD4 (SK3, Becton Dickinson, Franklin Lakes, NJ, USA), CD8 (SK1, Ebioscience, San Diego, CA, USA), CD45RO (UCHL1, BioLegend), CD62L (DREG-56, BioLegend) and PD1 (EH12.1, Becton Dickinson) were used. CD3suggested: (BD Biosciences Cat# 340571, RRID:AB_400474)CD4suggested: NoneCD8suggested: (Bethyl Cat# A810-007, RRID:AB_2891978)CD45ROsuggested: NoneUCHL1suggested: NoneCD62Lsuggested: NoneDREG-56suggested: NonePD1suggested: NoneSoftware and Algorithms Sentences Resources FACS data analysis and statistics: Flow cytometric data analysis was conducted with FlowJo 10 (Becton Dickinson). FlowJosuggested: (FlowJo, RRID:SCR_008520)Statistical examination and composition of ELISA and FACS data derived graphs were performed using GraphPad Prism 8 (GraphPad, La Jolla, CA, USA). GraphPad Prismsuggested: (GraphPad Prism, RRID:SCR_002798)GraphPadsuggested: (GraphPad Prism, RRID:SCR_002798)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:We recently reported that vaccine-specific CD4+ T cells in KTR show broad quantitative and functional limitations 6. In line with data on specific B cells presented herein, spike-reactive T cell frequencies were largely unaffected by a third vaccination. In accordance with the fact that an additional boost does not substantially expand the specific T cell pool in KTR, signs of ex vivo activation, as mirrored by high Ki67 or PD1 expression 6, were significantly reduced after the third dose as compared to the second dose. For reasons that need to be explored further, humoral responders were characterized by a significant increase of spike-specific T cells, a finding supported by recent work of Sahin et al., demonstrating a strong correlation between specific T cell frequencies and antibody titers post vaccination 18. As opposed to their quantities, vaccine-reactive T cells underwent a functional maturation after the third dose with higher portions of IL-2+, IL-4+ and multifunctional cells. Whereas increased IL-4 secretion could lower the threshold for isotype switching to IgG 19, patients might potentially benefit from augmented polyfunctionality being associated with potent SARS-CoV-2 clearance 20. In our cohort, all but one patient received antimetabolite medication. These drugs have been shown to be main contributors to a diminished immune response against SARS-CoV-2 vaccination in solid organ recipients 21. One potential strategy to improve responder rates is to reduce immu...
Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
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Results from scite Reference Check: We found no unreliable references.
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