Fig. 1: Three mRNA vaccine doses overcome impaired SARS-CoV-2 neutralization breadth-potency in STM patients.

A Overview of cohort demographics. B Surrogate neutralization (% ACE2 binding inhibition) of ancestral SARS-CoV-2 RBD one month post second BNT162b2 or AZD1222 dose and post mRNA booster. Pie charts indicate the proportion of vaccinees for whom neutralization was (black) or was not (grey) detected. ACE2 inhibition above 20% was deemed detectable neutralization capacity, as described in methods. C Proportion of vaccinees for whom neutralization was detected for the indicated number of variants. Number in the center of each pie chart indicates the median number of variants neutralized. RBD-specific IgG responses across the panel of seven tested SARS-CoV-2 variants one month post D two or E three doses of the indicated vaccine regimen. F RBD-specific IgG breadth-potency curves and scores one-month post indicated vaccine regimen. The proportion of variant-specific responses above a given threshold MFI is indicated by thin dashed lines for individual vaccinees. Group-specific mean proportions are indicated by thick dashed lines. Thick solid lines (breadth-potency curves) indicate the proportion vaccinees for whom the geometric mean response across variants is at or above a given threshold MFI. G RBD-specific IgG breadth-potency scores one-month post dose 2 and dose 3 for BNT162b2- and AZD1222-primed vaccinees. Black: Controls; Red: BNT162b2-primed STM; Blue: AZD1222-primed STM. Box plots represent median and IQR. Horizontal dotted lines indicate positivity threshold, calculated as described in methods. Statistical differences in proportions of vaccinees with (B) detectable surrogate neutralization and C) number of variants neutralized determined via chi-square test. Unpaired, nonparametric rank order comparisons between STM and control vaccinees or between dose 2 and dose 3 responses within each vaccinee regimen determined via Mann-Whitney U-tests. P < 0.0001 (****); P < 0.001 (***); P < 0.01 (**); P < 0.05 (*); non-significant (ns). MFI: median fluorescence intensity.