Fig. 3: Peripheral B cell responses to XBB.1.5 infection.

A Serum neutralizing titers after XBB.1.5 infection against SARS-CoV-2 WA-1 and Omicron BA.4/5 (n = 3–12 biological replicates per group). B Fold increase in neutralization titers four weeks after infection compared to pre-infection titers (n = 3–12 biological replicates per group). C, D Neutralization of WA-1 and different Omicron sublineages before and after XBB.1.5 infection (C) and the fold increase in neutralizing titers four weeks after infection compared to pre-infection titers (D) (n = 3–12). E Representative flow cytometry plots depicting WA-1 and BA.5 S specificity of the IgG memory B cells before and after XBB.1.5 infection. F Cumulative frequency of Spike-specific IgG memory B cells in the blood before and after XBB.1.5 infection (n = 3–12). G Frequencies of IgG memory B cells of different specificities in the blood before and after XBB.1.5 infection (n = 3–12). H Fold increase in IgG memory B cells of different specificities two weeks after XBB.1.5 infection compared to pre-infection (n = 3–12 biological replicates per group). I Schematic representation of competition ELISA assay to evaluate the proportion of antibodies binding epitopes present on BA.5 but not WA-1 RBD. J Binding of plasma IgG antibodies to BA.5 RBD with and without depletion of WA-1 RBD-specific antibodies, two weeks after bivalent booster and XBB.1.5 infection (n = 3–12 biological replicates per group). K Peak sgN viral loads in the nasal cavity and lungs of animals with no evidence of de novo response against BA.5 RBD (n = 11) and the ones with remaining detectable BA.5 binding after depletion with WA-1 RBD in post-infection samples (n = 4). Data is presented as geometric mean ± geometric SD (A, B, D, H) or arithmetic mean ± SEM (F). Horizontal dotted line represents a lower level of detection (A, C, J, K) or a fold change of 1 (B, D, H). Statistical analysis was performed using a non-parametric Kruskal-Wallis test with Dunn’s correction for multiple analysis (B, H, K). LLOD lower level of detection. Source data are provided as a Source Data file.