Fig. 6: Characterization of our cohort of vaccinees based on vaccine responsiveness and the associated extrafollicular-like signature.

a, Mean values of RBD IgG titers based on the classification of three groups: V_NL (MFI 0–10,000), V_M (MFI 10,000–100,000) and V_H (MFI >100,000); the proportion of responders is shown for each group (HD: filled squares, SLE: empty triangles) and vaccination time point. The number of samples analyzed (n) is shown at the bottom of the plots. b, Plasma log₁₀(NT₅₀) values detected for the pseudoviral neutralization of the WA.1 strain and based on the three groups of vaccine reactiveness as in a, at the Vax2 and Vax3 time points. The red lines in the plots indicate the LOS. The range of response (negative, low, medium, high) is indicated in the graphs. Each dot in the box plots represents an individual sample tested. Horizontal lines indicate the median. The proportion of positive responders is shown as the frequency indicated for each group and compared between groups of responders and time points (a two-sided Mann–Whitney U test was applied to compare the groups in the HD and SLE cohorts). c, Simple model showing the proposed B cell differentiation alongside the extrafollicular or GC pathways. Cell population frequencies were used to mimic a circulating B and T cell extrafollicular-derived signature based on reduced frequency of CD21⁺CD11c⁻ DN1 cells (<50%) and act cT_FH (CXCR5⁺PD-1⁺CD38⁺) cells (<1.4%) and increased frequency of CD21⁻CD11c⁺ DN2 cells (>20%), CD20⁻CD38^hi plasmablasts/plasma cells (>3%) and act T_PH (CXCR5⁻PD-1⁺CD38⁺) cells (>4%). d, Variables related to the extrafollicular signature were scored and summed in each sample tested for the V_NL, V_M and V_H groups in the HD and SLE cohorts. Intracohort and intercohort statistical comparisons were performed with a chi-square test. e–g, Bubble plots showing the correlation of cellular immune responses and RBD IgG titers. The red lines in the plots indicate the LOS. The frequencies of spike⁺⁺ B cells (e), spike⁺⁺RBD⁺ B cells (f) and AIM⁺ cT_FH cells (g) are shown. h, Bar graphs related to e–g showing the quantitation of nonresponders (black filled bars, based on the LOS) and responders (white filled bars) separated for each vaccination time point and group (V_NL: black line, V_M: light blue line, V_H: pink line). A chi-square test was used for statistical comparisons. The LOS was based on median values of baseline + 2 × s.d. Not significant, P > 0.05; *P < 0.05; ***P < 0.001; ****P < 0.0001. SHM, somatic hypermutation; EF, extrafollicular; SLPB, short-lived plasmablast; LLPC, long-lived plasma cell; ND, not determined; NS, not significant.