BA.1-reactive antibodies displayed higher VH SHM loads than those observed in antibodies isolated one month following two-dose mRNA vaccination (median = 3 substitutions) and similar to that observed in antibodies isolated six months following primary infection (median = 8 substitutions) or one month following three-dose mRNA vaccination (median = 8 substitutions), consistent with prolonged antibody affinity maturation over time and the time elapsed from vaccination to breakthrough infection (Fig. 3E) (21, 26, 27). This evidence concerns the gene CFB and infection.