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

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...

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Published inFrontiers in immunology Vol. 13; p. 876306
Main Authors Paschold, Lisa, Klee, Bianca, Gottschick, Cornelia, Willscher, Edith, Diexer, Sophie, Schultheiß, Christoph, Simnica, Donjete, Sedding, Daniel, Girndt, Matthias, Gekle, Michael, Mikolajczyk, Rafael, Binder, Mascha
Format Journal Article
LanguageEnglish
Published Switzerland Frontiers Media S.A 09.05.2022
Subjects
B cell maturation
booster vaccination
COVID-19
delta
Immunology
omicron variant
SARS-CoV-2
COVID-19
delta
booster vaccination
B cell maturation
SARS-CoV-2
omicron variant
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Summary: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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Edited by: Marko Radic, University of Tennessee College of Medicine, United States
Reviewed by: Mats Bemark, University of Gothenburg, Sweden; Matthew H. Collins, Emory University, United States
This article was submitted to B Cell Biology, a section of the journal Frontiers in Immunology
ISSN:1664-3224
1664-3224
DOI:10.3389/fimmu.2022.876306