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

Frontiers in Immunology

Matthias Girndt¹  Mascha Binder²  Christoph Schultheiß²  Donjete Simnica²  Edith Willscher²  Lisa Paschold²  Sophie Diexer³  Bianca Klee³  Rafael Mikolajczyk³  Cornelia Gottschick³  Michael Gekle⁴  Daniel Sedding⁵ 

[1] Department of Internal Medicine II, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany;Department of Internal Medicine IV, Oncology/Hematology, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany;Institute for Medical Epidemiology, Biometrics and Informatics (IMEBI), Interdisciplinary Center for Health Sciences, Medical School of the Martin-Luther University Halle-Wittenberg, Halle (Saale), Germany;Julius Bernstein-Institute of Physiology, Faculty of Medicine, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany;Mid-German Heart Center, Department of Cardiology and Intensive Care Medicine, University Hospital, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany;

关键词: SARS-CoV-2;    COVID-19;    delta;    B cell maturation;    omicron variant;    booster vaccination;   

DOI  :  10.3389/fimmu.2022.876306

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown