Durability of immune response against omicron BA.2 and BA.4/5 and T cell responses after boosting with mRNA and adenoviral vector-based vaccines following heterologous CoronaVac/ChAdOx-1nCov-19 vaccination.

Heterologous vaccination with inactivated vaccine followed by adenoviral vector-based vaccine has shown superiority in enhancing immune response compared to homologous primary series. However, data comparing immunity decline after a third booster following heterologous CoronaVac/ChAdOx-1nCov-19 has been limited. Here, we assessed neutralizing activity against omicron variant and T cell response at 3 months monitoring in 96 individuals who received ChAdOx-1nCov-19, BNT162b2, or mRNA-1273 as a third dose following heterologous CoronaVac/ChAdOx-1nCov-19. Comparing the antibody levels at 3 and 1 month(s) after the third booster, the results showed a persistence of anti-RBD IgG in all vaccine regimens, with the IgG level waning slower in the ChAdOx-1nCov-19 boosted group (geometric mean ratio (GMR): 0.64 (95%CI: 0.59-0.70)) compared to the BNT162b2 (0.34 (95%CI:0.31-0.38)) and mRNA-1273 boosted groups (0.32 (95%CI: 0.29-0.36)). Neutralizing activity against omicron BA.2 and BA.4/5 dropped by 1.2 to 1.5-fold but remained detectable, with the highest level observed in the mRNA-1273 group, followed by BNT162b2 and ChAdOx-1nCov-19 groups, respectively. Furthermore, the number of individuals with T cell reactivity decreased in BNT162b2 and mRNA-1273 groups, while it increased in ChAdOx-1nCov-19 group at 3-month post-boost compared to 1 month. Data on the durability of immune response could help comprehensively optimize the booster vaccine strategy.