Fig. 5: Cross-reactivity of vaccine- and infection-elicited SARS-CoV-2 RBD-binding MBCs.

a,b, Frequency of Wu RBD-binding (grey), Omicron (BA.1, BA.2 and BA.5) RBD pool-binding (red) and cross-reactive (blue) MBCs from donors of cohorts i–iv, as measured by flow cytometry. Data are individual frequencies for each donor (a) and mean frequency ± s.d. for each cohort (n = 4–16 donors) (b). c, Analysis of cross-reactivity with the BQ.1.1 RBD of Omicron (BA.1, BA.2 and BA.5) RBD pool-binding (red bars in b) and Wu/Omicron (BA.1, BA.2 and BA.5) RBD pool-cross-reactive (CR) (blue bars in b) MBCs. Data are mean frequency ± s.d. for each cohort (n = 4–16 donors). d, Cumulative cross-reactivity with the Wu RBD and the Omicron BA.1, BQ.1.1 or XBB.1 RBDs of IgGs secreted from in vitro-stimulated MBCs, as measured by ELISA. Data are mean absorbance values with the blank subtracted from n = 2 replicates of MBC cultures analysed from donors in cohorts vii and viii approximately 3 months after receiving their last vaccine dose. RBD-directed IgGs inhibiting binding of ACE2 to the Wu RBD are depicted in red. The total number (n_MBC) and the number of ACE2-inhibiting (ACE2_inh) RBD-directed IgG-positive cultures are indicated on top of each graph. Percentages of total (black) and ACE2-inhibiting (red) Wu-binding, Omicron-binding and Wu/Omicron-cross-reactive IgG-positive cultures are indicated within each quadrant. e,f, Individual frequencies (e) and mean (± s.d.) frequencies for each cohort (n = 5–6 donors) (f) of Wu RBD-specific, Omicron-specific and RBD cross-reactive (BA.1, BQ.1.1 and XBB.1) IgG-positive cultures from donors of cohorts vii and viii.