Dynamic SARS-CoV-2-specific B-cell and T-cell responses following immunization with an inactivated COVID-19 vaccine

OBJECTIVE: The dynamic adaptive immune responses elicited by the inactivated virus vaccine CoronaVac remain elusive. METHODS: In a prospective cohort of 100 healthcare professionals naïve for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) who received two doses of CoronaVac, we analysed SARS-CoV-2-specific humoral and cellular responses at four different timepoints, including before vaccination (T1), 2 weeks after the first dose (T2), 2 weeks after the booster dose (T3), and 8–10 weeks after the booster dose (T4). SARS-CoV-2-specific antibodies, serum neutralizing activities, peripheral B cells, CD4(+) and CD8(+) T cells and their memory subsets were simultaneously measured in this cohort. RESULTS: SARS-CoV-2 spike-specific IgG responses reached a peak (geometric mean titre (GMT) 54827, 30969–97065) after two doses and rapidly declined (GMT 502, 212–1190) at T4, whereas suboptimal IgA responses were detected (GMT 5, 2–9). Spike-specific circulating B cells (0.60%, 0.46–0.73% of total B cells) and memory B cells (1.18%, 0.92–1.44% of total memory B cells) were effectively induced at T3 and sustained over time (0.33%, 0.23–0.43%; 0.87%, 0.05–1.67%, respectively). SARS-CoV-2-specific circulating CD4(+) T cells (0.57%, 0.47–0.66%) and CD8(+) T cells (1.29%, 1.04–1.54%) were detected at T3. At T4, 0.78% (0.43–1.20%) of memory CD4+ T cells and 0.68% (0.29–1.30%) of memory CD8+ T cells were identified as SARS-CoV-2-specific, while 0.62% (0.51–0.75%) of CD4(+) T cells and 0.47% (0.38–0.58%) of CD8(+) T cells were SARS-CoV-2-specific terminally differentiated effector memory cells. Furthermore, age and interval between doses affected the magnitude of CoronaVac-induced immune responses. SARS-CoV-2 memory CD4(+) T cells were strongly associated with both receptor binding domain (RBD)-specific memory B cells (r 0.87, p <0.0001) and SARS-CoV-2-specific memory CD8(+) T cells (r 0.48, p <0.0001). CONCLUSIONS: CoronaVac induced robust circulating and memory B cell and T cell responses. Our study offers new insight into the underlying immunobiology of inactivated virus vaccines in humans and may have implications for vaccine strategies in the future.