mRNA-based influenza vaccine expands the breadth of the B cell response in humans

In the draining lymph nodes, mRNA vaccination stimulated sustained GC reactions that persisted for at least 26 weeks post vaccination in five of thirteen participants across the two seasons. To understand how sustained GC activity shapes the secreted serum IgG repertoire, we performed proteomic analysis of serum IgG repertoire. mRNA vaccination increased the number of vaccine-elicited serum IgG clonotypes and promoted intraclonal expansion within pre-existing clonotypes.

B cell lineage analyses further indicated that expanded serum clonotypes map to GC B cell-associated subbranches, consistent with ongoing GC-driven evolution underlying intraclonal expansion. This repertoire remodeling was accompanied by increased binding breadth against antigenically divergent influenza viruses. These findings reveal a key role for persistent GC responses in broadening the repertoire of vaccine-induced antibodies.