Rapid Hypermutation B Cell Trajectory Recruits Previously Primed B Cells Upon Third SARS-Cov-2 mRNA Vaccination
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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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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
Ethics IRB: 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 variable not detected. Randomization Fifteen randomly chosen participants without prior COVID-19 infection donated blood prior to and on day 14 (d14) after booster vaccination at this data cut. Blinding not detected. Power Analysis not detected. Table 2: Resources
Antibodies Sentences Resources 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 … 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
Ethics IRB: 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 variable not detected. Randomization Fifteen randomly chosen participants without prior COVID-19 infection donated blood prior to and on day 14 (d14) after booster vaccination at this data cut. Blinding not detected. Power Analysis not detected. Table 2: Resources
Antibodies Sentences Resources 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/IgGsuggested: NoneAnti-SARS-CoV-2-NCP-ELISAsuggested: NoneSoftware and Algorithms Sentences Resources All statistical analyses were performed using R version 4.1.2 and GraphPad Prism 8.3.1 (GraphPad Software, La Jolla, CA, USA). GraphPad Prismsuggested: (GraphPad Prism, RRID:SCR_002798)GraphPadsuggested: (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.
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