Cellular immune response following homologous and heterologous BNT162b2 booster vaccination after primary immunization with BNT162b2 and CoronaVac respectively.

Several vaccines targeting SARS-CoV-2 were developed following the COVID-19 outbreak. However, subsequent studies have indicated that humoral immune responses wane over time, particularly with the emergence of new SARS-CoV-2 variants. There is limited understanding of the resilience of T cell-mediated immunity induced by COVID-19 vaccines. This prospective cohort study involved a population who completed two primary doses of either the Pfizer BNT162b2 mRNA vaccine (PP) or the Sinovac Coronavac inactivated virus vaccine (SS) followed by one homologous (PPP) or heterologous (SSP) booster dose of BNT162b2, through convenience sampling of healthy adults. Blood samples were collected at three intervals, 2-weeks (T1), 6-8 months (T2), and 12-months (T3) following the booster immunization. Immunophenotyping was performed to evaluate T cell activity, memory, and intracellular cytokines at each timepoint. Our study found that the expression of T cell activation markers by both CD4+ and CD8+ T cells, such as CD25 + CD69+ and CD38 + HLA-DR+ was significantly higher at T2 compared to T1 in both PPP and SSP groups, indicating a robust T cell activation post-booster vaccination. Memory T cell subsets, including central memory and stem cell memory T cells, exhibited distinct kinetics, with both vaccines showing sustained levels of selected memory T cell subsets right up to about one year after booster. Furthermore, intracellular cytokine analysis revealed that CD4+ and CD8+ T cells in the SSP group exhibited higher level of IL-2, TNF-α and IFN-γ at specific timepoints, suggesting a stronger cellular immune response. These findings highlight the durability and qualitative differences in T cell-mediated immunity between homologous and heterologous vaccination regimens. While cellular immunity persisted in both groups up to 12 months post-booster, a decline in T3 underscores the potential, targeted need for additional booster doses to maintain protection against emerging SARS-CoV-2 variants.