Adolescents have boosted and non-inferior humoral immune responses to the WT virus in comparison to adults after the third dose of the BNT162b2 vaccine. Humoral responses were compared at pre-dose 1, post-dose 2 (1 month after dose 2), pre-dose 3 (5 months after dose 2) and post-dose 3 (3 weeks after booster) in evaluable adolescents. a Longitudinal analysis of S IgG (pre-dose 1 N = 12, post-dose 2 N = 21, pre-dose 3 N = 21, post-dose 3 N = 21), S-RBD IgG (pre-dose 1 N = 21, post-dose 2 N = 21, pre-dose 3 N = 21, post-dose 3 N = 21), sVNT inhibition (pre-dose 1 N = 21, post-dose 2 N = 21, pre-dose 3 N = 21, post-dose 3 N = 18), PRNT90 (pre-dose 1 N = 9, post-dose 2 N = 9, pre-dose 3 N = 9, post-dose 3 N = 9), PRNT50 (pre-dose 1 N = 9, post-dose 2 N = 9, pre-dose 3 N = 9, post-dose 3 N = 9), S IgG avidity (pre-dose 1 N = 0, post-dose 2 N = 21, pre-dose 3 N = 20, post-dose 3 N = 21) and S IgG FcγRIIIa-binding (pre-dose 1 N = 12, post-dose 2 N = 21, pre-dose 3 N = 21, post-dose 3 N = 21) in evaluable adolescents. A third dose booster increased humoral responses except for S IgG FcγRIIIa-binding. Importantly, S IgG, S-RBD IgG, PRNT50 and S IgG avidity were higher post-dose 3 compared to post-dose 2, while there was a reduction in S IgG FcγRIIIa-binding. Longitudinal analysis was determined using paired t-test after natural logarithmic transformation with p values denoted. Dots representing the same participants are linked by a straight line. Data labels and centre lines show geometric means (GM) estimates, with corresponding 95% confidence intervals shown by error bars. b Non-inferiority testing of S IgG (adolescent N = 28, adult N = 28), S-RBD IgG (adolescent N = 28, adult N = 33), sVNT inhibition (adolescent N = 25, adult N = 33), PRNT90 (adolescent N = 14, adult N = 14), PRNT50 (adolescent N = 14, adult N = 14), S IgG avidity (adolescent N = 28, adult N = 28) and S IgG FcγRIIIa-binding (adolescent N = 28, adult N = 28) in evaluable adolescents in comparison to adults. These humoral responses were non-inferior, except for S IgG avidity, which was non-inferior and superior. Geometric mean ratios and their associated two-sided 95% confidence intervals (CIs) were plotted. There was no associated 95% CI for PRNT50, as all values in both groups were equal, at the upper LOD of 320. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001. ns not significant. LOD limits of detection, LOQ limits of quantification, WT wild-type, S-RBD spike-receptor-binding domain, sVNT surrogate virus neutralisation test, PRNT plaque reduction neutralisation test, FcγRIIIa Fcγ receptor IIIa