a, Schematic illustration of the spike mutation profiles of B.1, Alpha, Delta and Beta. NTD, N-terminal domain; RBD, receptor binding domain. b,c, Neutralization of pseudotypes bearing the SARS-CoV-2 B.1, Alpha, Delta or Beta spike by sera (n = 37 biologically independent samples) were compared in age-stratified cohorts: 70–79 years (n = 24, solid circles) (b) and 80–89 years (n = 13, open circles) (c). Statistical comparison of ND80 titres at 3 and 20 weeks was performed using a Wilcoxon two-tailed matched-pairs signed rank test (***P < 0.001; ****P < 0.0001; NS, not significant). Fold changes in median ND80 compared with B.1 are indicated (lower detection limit = 10 (dotted line), upper detection limit = 2,560 for Delta, 7,290 for B.1, Alpha, Beta). Medians are indicated with a solid line and upper and lower quartiles with dashed lines within the violin plots. d–f, The correlation between ND80 and S ELISA (S Roche) titres for each volunteer (n = 37) was examined (d), with statistical analysis performed using a non-parametric two-tailed Spearman correlation (r). The same sera (70–79; n = 24, solid circles (e) and 80–89; n = 13, open circles (f)) was analysed with RBD-based ELISA assays, representing B.1, Alpha, Beta and Delta spikes. Horizontal lines represent the median. The equation for determining titre is described in the Methods (RBD-ELISA). Statistical comparison of RBD-ELISA titres was performed using a Friedman test with Dunn’s multiple comparisons of column means (**P < 0.005; ****P < 0.0001). Fold changes in median titre compared with B.1 are indicated. The lower detection limit of the assay is defined as 100 (dotted line). The upper detection limit is defined as 129,600. g,h, The correlation between B.1 RBD-ELISA and S ELISA titres (S Roche) (g) or ND80 titres and the respective RBD-ELISA data for each VOC (h) recorded from each volunteer (n = 37) was then examined, with statistical analysis performed using a non-parametric two-tailed Spearman correlation (r).