Abstract
The present study investigated T and B cell responses following a second heterologous booster dose of BNT162b2 administered after a two-dose CoronaVac regimen for coronavirus disease 2019 (COVID-19) vaccination in 15 healthcare workers. Blood samples were collected 4 weeks after the first booster and at both 4 and 24 weeks after the second BNT162b2 booster. Interferon-γ-secreting CD4+ and CD8+ T cells were detectable 4 weeks after the first booster, whereas only CD4+ T cells remained detectable at both 4 and 24 weeks after the second booster. Seven of the 15 participants (46.7%) were diagnosed with COVID-19 approximately 16 weeks after receiving the second booster. These individuals exhibited significantly higher frequencies of CD4+ T cells at 24 weeks post-booster than at 4 weeks post-booster. In contrast, the non-COVID-19 group exhibited significantly higher CD4+ T cell responses 4 weeks after the second booster. Memory B cells were detected at low frequencies at all three time points. IgG antibodies against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein were detectable at all three time points, with a significant decline observed 24 weeks after the second booster. Overall, CD4+ T and B cell responses induced by a heterologous second booster dose of BNT162b2 following a primary two-dose CoronaVac regimen were rapidly elicited and sustained for at least 6 months.IMPORTANCEThere is limited evidence regarding T and B cell responses following a primary COVID-19 vaccination series with CoronaVac and two heterologous BNT162b2 booster doses. This study investigated the longitudinal T and B cell responses induced by a second heterologous BNT162b2 booster following a primary two-dose CoronaVac COVID-19 vaccination regimen. These results demonstrate that CD4+ T cells induced by the second heterologous BNT162b2 booster play a key role in protection against SARS-CoV-2 infection and progression to severe disease. This study suggests the need for the future consideration of repeated emergency vaccine-boosting strategies in response to emerging viral infections.