Fig. 1: Comparison of immune responses prior to omicron infection in vaccinated SARS-CoV-2-naive and previously-infected individuals.

Samples were taken a median of 32 days (IQR 28-42.3) after 3rd mRNA dose. a Live-virus neutralizing activity of plasma against ancestral, BA.1, BA.2, and BA.5 viruses, expressed as the reciprocal of the dilution showing 50% reduction in focus forming units (FRNT50); SARS-CoV-2 spike-specific binding IgG (b) and IgA (c) in plasma against ancestral, BA.2 and BA.5 spike proteins (AU/mL = arbitrary antibody units/mL in MesoScale Discovery (MSD) assay); d nucleocapsid-specific IgG in plasma, assessed by ELISA and expressed in WHO International units, BAU/mL; Secretory IgA (sIgA) in nasal lining fluid targeting (e) ancestral, BA.1, BA.2, and BA.4 spike proteins and f nucleocapsid-specific sIgA, expressed as area under the curve (AUC) normalized to total sIgA; g ability of nasal lining fluid to inhibit ACE2 binding to ancestral, BA.2 and BA.5 spike proteins, assessed by MSD assay; IFN-γ ELISpot responses to overlapping peptide pools representing the S1 (h) and S2 (i) spike subunits of ancestral, BA.1 and BA.2 viruses, and j a single-pool-containing peptides of both the ancestral membrane (M) and nucleocapsid (N) proteins. Results are expressed as spot-forming units per million cells (SFU/10⁶). The dashed line represents a positivity threshold of the mean + 2 SD of the background response. Data are shown with median and interquartile range. Median fold-difference between infection-naive and previously-infected individuals is displayed. All comparisons were made with two-sided Mann–Whitney U-test. p-values are displayed where <0.05. For a–d, responses were evaluated in 53 SARS-CoV-2-naive and 37 previously-infected individuals for whom samples were available. For e–g, responses were evaluated in 32 SARS-CoV-2-naive and 19 previously-infected individuals for whom samples were available. For h–j, responses were evaluated in 37 SARS-CoV-2-naive and 32 previously-infected individuals for whom samples were available. Source data are provided as a Source Data file.