Rapid hypermutation B cell trajectory recruits previously primed B cells upon third SARS-CoV-2 mRNA vaccination

Paschold, L.; Klee, B.; Gottschick, C.; Willscher, E.; Diexer, S.; Schultheiss, C.; Simnica, D.; Sedding, D.; Girndt, M.; Gekle, M.; Mikolajczyk, R.; Binder, M.

doi:10.1101/2022.03.01.482462

bioRxiv · 10.1101/2022.03.01.482462

Rapid hypermutation B cell trajectory recruits previously primed B cells upon third SARS-CoV-2 mRNA vaccination

Paschold, L.·Klee, B.·Gottschick, C.·Willscher, E.·Diexer, S.·Schultheiss, C.·Simnica, D.·Sedding, D.·Girndt, M.·Gekle, M.·Mikolajczyk, R.·Binder, M.

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Abstract

High antibody affinity against the ancestral SARS-CoV-2 strain seems to be necessary (but not always sufficient) for the control of emerging immune-escape variants. Therefore, aiming at strong B cell somatic hypermutation - not only at high antibody titers - is a priority when utilizing vaccines that are not targeted at individual variants. 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 naive, 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 booster, but not the primary vaccination series, offers some protection against immune-escape variants such as Omicron B.1.1.529. Brief summaryPriming SARS-CoV-2 vaccinations generate antibodies from low-level matured B cells while the third vaccination strongly boosts somatic hypermutation potentially explaining different protection from immune-escape variants.

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Paschold, L., Klee, B., Gottschick, C., Willscher, E., Diexer, S., Schultheiss, C., Simnica, D., Sedding, D., Girndt, M., Gekle, M., Mikolajczyk, R., Binder, M.. 2022-03-02. Rapid hypermutation B cell trajectory recruits previously primed B cells upon third SARS-CoV-2 mRNA vaccination. https://doi.org/10.1101/2022.03.01.482462

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