Tracking B cell responses to the SARS-CoV-2 mRNA-1273 vaccine

Protective immunity following vaccination is sustained by long-lived antibody-secreting cells and resting memory B cells (MBCs). Responses to two-dose SARS-CoV-2 mRNA-1273 vaccination are evaluated longitudinally by multimodal single-cell analysis in three infection-naïve individuals. Integrated surface protein, transcriptomics, and B cell receptor (BCR) repertoire analysis of sorted plasmablasts and spike+ (S-2P+) and S-2P− B cells reveal clonal expansion and accumulating mutations among S-2P+ cells. These cells are enriched in a cluster of immunoglobulin G-expressing MBCs and evolve along a bifurcated trajectory rooted in CXCR3+ MBCs. One branch leads to CD11c+ atypical MBCs while the other develops from CD71+ activated precursors to resting MBCs, the dominant population at month 6. Among 12 evolving S-2P+ clones, several are populated with plasmablasts at early timepoints as well as CD71+ activated and resting MBCs at later timepoints, and display intra- and/or inter-cohort BCR convergence. These relationships suggest a coordinated and predictable evolution of SARS-CoV-2 vaccine-generated MBCs. [Display omitted] •Clonally related spike-specific plasmablasts and memory B cells•Durable resting memory B cells arise from CD71+ activated B cells•Incremental accumulation of BCR somatic mutations•Evidence of convergence and common differentiation pathways Using multiomic single-cell analyses, Assis et al. show a coordinated trajectory involving plasmablasts and activated and resting memory B cells in response to primary SARS-CoV-2 mRNA vaccination. Spike-specific BCR repertoire analysis shows incremental affinity maturation across the 6-month study period and reveals evidence of convergence among study participants and other cohorts.