Neutralizing antibody and T cell responses of individuals who received a homologous (BNT-primed + BNT) (n = 14) booster and those who subsequently experienced breakthrough infection (n = 11), and heterologous (ChAd-primed + BNT) (n = 15) booster. (A) Longitudinal study design. Blood samples were collected before booster (B1), and 21 days (B2), 3 months (B3), and 6 months (B4) after the booster. For homologous booster breakthrough group, B4 sample was collected at 61–93 days after breakthrough infection. (B) Neutralizing antibody titers (log IC50) against pseudoviruses bearing wild type (WT) or Omicron spike proteins. Significant differences within groups were assessed with the two-tailed Wilcoxon matched-pair sum ranked test. The horizontal lines represent neutralizing antibody titers of individual samples collected at time-points against WT (light blue) and Omicron (light pink). The dark blue (WT) and dark pink (Omicron) lines represent the geometric means of log transformed values. P values in blue and pink represent significant differences in neutralizing antibody titers against WT and Omicron, respectively. The numbers in parentheses represent the GMT fold changes in neutralization against Omicron compared with WT and significant p values are stated above the fold change numbers. (C) Comparison of the GMT ± 95% confidence intervals against WT or Omicron spike. Significant differences between groups were assessed using the Mann–Whitney U-test. Significant p values for each comparison are shown. All experiments were performed in duplicate. (D) T cell immune responses against QuantiFeron SARS-CoV-2 Ag1, Ag2 and Ag3. Interferon-ɣ levels measured were normalized against the nil tube value (background). The Wilcoxon matched-pairs signed rank test was used to determine the significant differences within groups. Comparison between homologous booster, homologous booster breakthrough and heterologous booster groups at the same time-points were assessed using the Mann–Whitney U-test. Responses are shown as dot plots with connecting horizontal lines to represent interferon-ɣ changes in individual samples. The bold lines represent the medians of the interferon-ɣ responses.