CD19+IgD+CD27- Naïve B Cells as Predictors of Humoral Response to COVID 19 mRNA Vaccination in Immunocompromised Patients

  1. Eduard Schulz
  2. Isabel Hodl
  3. Patrick Forstner
  4. Stefan Hatzl
  5. Nazanin Sareban
  6. Martina Moritz
  7. Johannes Fessler
  8. Barbara Dreo
  9. Barbara Uhl
  10. Claudia Url
  11. Andrea J. Grisold
  12. Michael Khalil
  13. Barbara Kleinhappl
  14. Christian Enzinger
  15. Martin H. Stradner
  16. Hildegard T. Greinix
  17. Peter Schlenke
  18. Ivo Steinmetz

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Abstract

Immunocompromised patients are considered high-risk and prioritized for vaccination against COVID-19. We aimed to analyze B-cell subsets in these patients to identify potential predictors of humoral vaccination response. Patients (n=120) suffering from hematologic malignancies or other causes of immunodeficiency and healthy controls (n=79) received a full vaccination series with an mRNA vaccine. B-cell subsets were analyzed prior to vaccination. Two independent anti-SARS-CoV-2 immunoassays targeting the receptor-binding domain (RBD) or trimeric S protein (TSP) were performed three to four weeks after the second vaccination. Seroconversion occurred in 100% of healthy controls, in contrast to 67% (RBD) and 82% (TSP) of immunocompromised patients, while only 32% (RBD) and 22% (TSP) achieved antibody levels comparable to those of healthy controls. The number of circulating CD19 + IgD + CD27 - naïve B cells was strongly associated with antibody levels (ρ=0.761, P<0.001) and the only independent predictor for achieving antibody levels comparable to healthy controls (OR 1.07 per 10-µL increase, 95%CI 1.02–1.12, P=0.009). Receiver operating characteristic analysis identified a cut-off at ≥61 naïve B cells per µl to discriminate between patients with and without an optimal antibody response. Consequently, measuring of naïve B cells in immunocompromised hematologic patients could be useful in predicting their humoral vaccination response.

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  1. Version published to 10.3389/fimmu.2021.803742
  2. Version published to 10.1101/2021.08.11.21261898v2 on medRxiv
  3. ScreenIT

    SciScore for 10.1101/2021.08.11.21261898: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    EthicsIRB: After approval by the ethics committee of the Medical University of Graz in April 2021 (EK 1128/2021), patients with inborn errors of immunity, hematological malignancies, those receiving B-cell-depleting therapy, and healthy controls were recruited before receiving their first dose of COVID-19 vaccine.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    One million PBMCs were incubated with the following antibodies: CD19-VioGreen, anti-IgD-VioBlue, CD24-PerCP-Vio700, CD38-FITC, CD27-APC, CD86-PE-Vio770, CD21-APC-Vio770, and anti-IgM-PE (Miltenyi Biotec, Bergisch Gladbach, Germany).
    anti-IgD-VioBlue
    suggested: (Miltenyi Biotec Cat# 130-099-487, RRID:AB_2659774)
    CD21-APC-Vio770
    suggested: None
    anti-IgM-PE (Miltenyi Biotec, Bergisch Gladbach, Germany).
    suggested: None
    Two CE-marked serological tests were performed according to the manufacturers’ protocols to determine and quantify specific antibodies against SARS-CoV-2. A Specific IgG was determined using the Roche Elecsys anti-SARS-CoV-2 S electrochemiluminescence immunoassay targeting the receptor-binding domain of the viral spike protein using a Cobas e 801 analytical unit (Roche Diagnostics GmbH, Mannheim, Germany).[20, 24] Its quantification range lies between 0.4 and 2500 U/mL, with a cut-off of 0.8 U/mL for positivity.
    anti-SARS-CoV-2
    suggested: None

    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:
    In a larger cohort, Mrak et al. found that the time since the last rituximab treatment correlated with B-cell frequency but was not an independent predictor of seroconversion.[24] Our study had several limitations. These include single-center design and limited representation of some patient cohorts that do not allow clear conclusions on seroconversion rates among less common entities or less frequently used treatment strategies. Moreover, we cannot make any statements about the persistence of the vaccination response at this point. Our study relies on the measurement of antibodies as a surrogate for immunity to COVID-19. However, our results do not significantly differ between the two internationally deployed anti-spike protein serological assays for detecting either total IgG or IgG. Both tests showed a high correlation with surrogate neutralization tests, and Roche’s assay correlated well with live virus neutralization tests in vaccinated individuals.[24, 26] The strength of our study is its prospective design and the introduction of the stringent vaccination response as a potentially more relevant concept than seroconversion. In summary, the humoral response to the SARS-CoV-2 mRNA vaccine is impaired in immunocompromised patients. The abundance of circulating naïve B cells is strongly associated with a normal antibody vaccine response across different conditions and therapies. Therefore, measuring naïve B cells may predict the humoral response to COVID-19 vaccination. Fur...

    Results from TrialIdentifier: We found the following clinical trial numbers in your paper:

    IdentifierStatusTitle
    NCT04858607RecruitingHumoral and Cellular Immune Response to COVID-19 Vaccines in…

    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.

    About SciScore

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  4. Version published to 10.1101/2021.08.11.21261898v1 on medRxiv