Rapid Hypermutation B Cell Trajectory Recruits Previously Primed B Cells Upon Third SARS-Cov-2 mRNA Vaccination

  1. Lisa Paschold
  2. Bianca Klee
  3. Cornelia Gottschick
  4. Edith Willscher
  5. Sophie Diexer
  6. Christoph Schultheiß
  7. Donjete Simnica
  8. Daniel Sedding
  9. Matthias Girndt
  10. Michael Gekle
  11. Rafael Mikolajczyk
  12. Mascha Binder

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Abstract

The COVID-19 pandemic shows that vaccination strategies building on an ancestral viral strain need to be optimized for the control of potentially emerging viral variants. Therefore, aiming at strong B cell somatic hypermutation to increase antibody affinity to the ancestral strain - not only at high antibody titers - is a priority when utilizing vaccines that are not targeted at individual variants since high affinity may offer some flexibility to compensate for strain-individual mutations. Here, we developed a next-generation sequencing based SARS-CoV-2 B cell tracking protocol to rapidly determine the level of immunoglobulin somatic hypermutation at distinct points during the immunization period. The percentage of somatically hypermutated B cells in the SARS-CoV-2 specific repertoire was low after the primary vaccination series, evolved further over months and increased steeply after boosting. The third vaccination mobilized not only naïve, but also antigen-experienced B cell clones into further rapid somatic hypermutation trajectories indicating increased affinity. Together, the strongly mutated post-booster repertoires and antibodies deriving from this may explain why the third, but not the primary vaccination series, offers some protection against immune-escape variants such as Omicron B.1.1.529.

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  1. Version published to 10.3389/fimmu.2022.876306
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    SciScore for 10.1101/2022.03.01.482462: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: The study was approved by the institutional review board (approval number 2020-076).
    Consent: Informed written consent was obtained and the study was approved by the institutional review board (approval number 2020-039).
    Sex as a biological variablenot detected.
    RandomizationFifteen randomly chosen participants without prior COVID-19 infection donated blood prior to and on day 14 (d14) after booster vaccination at this data cut.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    SARS-CoV-2 antibody profiling: Antibodies against the S1 domain of the spike (S) protein and the nucleocapsid protein (NCP) of SARS-CoV-2 were determined by Anti-SARS-CoV-2-ELISA IgA/IgG and Anti-SARS-CoV-2-NCP-ELISA kits from Euroimmun (Lübeck, Germany).
    Anti-SARS-CoV-2-ELISA IgA/IgG
    suggested: None
    Anti-SARS-CoV-2-NCP-ELISA
    suggested: None
    Software and Algorithms
    SentencesResources
    All statistical analyses were performed using R version 4.1.2 and GraphPad Prism 8.3.1 (GraphPad Software, La Jolla, CA, USA).
    GraphPad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)
    GraphPad
    suggested: (GraphPad Prism, RRID:SCR_002798)

    Results from OddPub: Thank you for sharing your data.

    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.
    • Thank you for including a protocol registration statement.

    Results from scite Reference Check: We found no unreliable references.

    About SciScore

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  3. Version published to 10.1101/2022.03.01.482462v1 on bioRxiv