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.
Keywords: B cell maturation; COVID-19; SARS-CoV-2; booster vaccination; delta; omicron variant.
【저자키워드】 COVID-19, SARS-CoV-2, Delta, omicron variant., booster vaccination, B cell maturation, 【초록키워드】 Vaccine, vaccination, protocol, antibody, COVID-19 pandemic, mutations, variant, omicron, immunization, Antigen, B cell, Viral, Immunoglobulin, Next-generation sequencing, Vaccination strategies, Antibody titer, Viral variants, trajectory, Omicron variant, B.1.1.529, Antibody titers, booster, booster vaccination, strain, Vaccination strategy, antibody affinity, viral strain, priority, high affinity, naïve, clone, offer, determine, mutated, explain, the SARS-CoV-2, 【제목키워드】 mRNA, Rapid, hypermutation,