Cellular and humoral immune responses following SARS-CoV-2 mRNA vaccination in patients with multiple sclerosis on anti-CD20 therapy
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Abstract
SARS-CoV-2 messenger RNA vaccination in healthy individuals generates immune protection against COVID-19. However, little is known about SARS-CoV-2 mRNA vaccine-induced responses in immunosuppressed patients. We investigated induction of antigen-specific antibody, B cell and T cell responses longitudinally in patients with multiple sclerosis (MS) on anti-CD20 antibody monotherapy ( n = 20) compared with healthy controls ( n = 10) after BNT162b2 or mRNA-1273 mRNA vaccination. Treatment with anti-CD20 monoclonal antibody (aCD20) significantly reduced spike-specific and receptor-binding domain (RBD)-specific antibody and memory B cell responses in most patients, an effect ameliorated with longer duration from last aCD20 treatment and extent of B cell reconstitution. By contrast, all patients with MS treated with aCD20 generated antigen-specific CD4 and CD8 T cell responses after vaccination. Treatment with aCD20 skewed responses, compromising circulating follicular helper T (T FH ) cell responses and augmenting CD8 T cell induction, while preserving type 1 helper T (T H 1) cell priming. Patients with MS treated with aCD20 lacking anti-RBD IgG had the most severe defect in circulating T FH responses and more robust CD8 T cell responses. These data define the nature of the SARS-CoV-2 vaccine-induced immune landscape in aCD20-treated patients and provide insights into coordinated mRNA vaccine-induced immune responses in humans. Our findings have implications for clinical decision-making and public health policy for immunosuppressed patients including those treated with aCD20.
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SciScore for 10.1101/2021.06.23.21259389: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics Consent: All subjects enrolled in this study provided informed consent as part of protocols approved by the University of Pennsylvania Institutional Review Boards (IRBs) and in compliance with the Declaration of Helsinki principles.
IRB: All subjects enrolled in this study provided informed consent as part of protocols approved by the University of Pennsylvania Institutional Review Boards (IRBs) and in compliance with the Declaration of Helsinki principles.Sex as a biological variable not detected. Randomization not detected. Blinding All experiments were conducted in a blinded fashion with designated members of the clinical team (that were not part of running the assays) having access to the … SciScore for 10.1101/2021.06.23.21259389: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics Consent: All subjects enrolled in this study provided informed consent as part of protocols approved by the University of Pennsylvania Institutional Review Boards (IRBs) and in compliance with the Declaration of Helsinki principles.
IRB: All subjects enrolled in this study provided informed consent as part of protocols approved by the University of Pennsylvania Institutional Review Boards (IRBs) and in compliance with the Declaration of Helsinki principles.Sex as a biological variable not detected. Randomization not detected. Blinding All experiments were conducted in a blinded fashion with designated members of the clinical team (that were not part of running the assays) having access to the sample key until the data were collected, at which point all researchers were unblinded for the analysis. Power Analysis not detected. Table 2: Resources
Antibodies Sentences Resources After the rest, CD40 blocking antibody (0.5mg/mL final concentration) was added to cultures for 15 minutes prior to stimulation, and cells were subsequently stimulated for 24 hours with costimulation (anti-human CD28/CD49d, BD Biosciences) and peptide megapools (CD4-S for all CD4 T cell analyses, CD8-E for all CD8 T cell analyses) at a final concentration of 1 mg/mL. CD40suggested: Noneanti-human CD28/CD49dsuggested: None20 hours post-stimulation, antibodies targeting CXCR3, CCR7, CD40L, CXCR5, and CCR6 were added to the culture along with monensin (GolgiStop, BD Biosciences) for a four hour stain at 37°C. CXCR3suggested: NoneCCR7suggested: NoneCXCR5suggested: NoneCCR6suggested: NoneSurface staining for 30 minutes at room temperature was then performed with antibodies directed against CD4, CD8, CD45RA, CD27, CD3, CD40L, CD200, and 41BB in FACS buffer. CD4suggested: NoneCD8suggested: (Fitzgerald Industries International Cat# 61R-CD154dHUBT, RRID:AB_1283044)CD45RAsuggested: NoneCD27suggested: NoneCD3suggested: NoneCD40Lsuggested: NoneCD200suggested: NoneSoftware and Algorithms Sentences Resources High-dimensional data analysis of flow cytometry data: Opt-SNE and FlowSOM analyses were performed using OMIQ ( FlowSOMsuggested: (FlowSOM, RRID:SCR_016899)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: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.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.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
Results from scite Reference Check: We found no unreliable references.
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