SARS-CoV-2 booster vaccines enhance antibody responses. In Nature, Alsoussi et al. analyze lymph nodes (weeks 2 and 8), blood (week 17) and bone marrow (week 26) from vaccinated, COVID-19-naive individuals boosted with an ancestral or a bivalent Beta–Delta mRNA vaccine (dose 3), and show that memory B cells are efficiently re-engaged into germinal center reactions. In three individuals for which data were available on the B cell responses to the primary vaccination (post-dose 2), single-cell RNA sequencing indicated a clonal relationship between the plasma cells induced by the primary vaccine and the lymph node germinal center B cells, circulating memory B cells and bone marrow plasma cells induced by dose 3, with some, but not all clones showing increased somatic hypermutation after dose 3. Of the monoclonal antibodies isolated from individuals boosted with the ancestral, Beta–Delta or an Omicron vaccine (dose 4 after a Beta–Delta dose 3), 61%, 57% or 71% recognized Omicron, respectively. Among the isolated antibodies, none specifically recognized Beta or Delta without cross-reacting to the ancestral strain, whereas the antibodies that bound specifically to Omicron had low somatic hypermutation. This indicates that memory B cells generated in the primary vaccination dominate the recall response, even to variant-based boosters.

Original reference: Nature (2023).