Kinetics of SARS-CoV-2 Spike Antibodies after the Second and Third Dose of the BNT162b2 COVID-19 Vaccine and Association with Epidemiological Characteristics and Breakthrough Infection in a Cohort Study of Healthcare Workers

To prospectively study the kinetics of immune responses after immunization with the BNT162b2 mRNA COVID-19 vaccine and their association with epidemiological parameters and breakthrough infection (BI), we measured total (TAbs-WT) and neutralizing antibodies against wild-type (NAbs-WT) and Omicron (NAbs-O) SARS-CoV-2 spike proteins in healthcare workers (HCWs) after the second (4 and 8 months) and third dose (1 and 8 months). Vaccinated HCWs (n = 486), with a median age (IQR) of 49 years (38–56), were included in this prospective cohort study. BI was observed 4 and 8 months after the second dose in 8/486 (1.6%) and 15/486 (3.1%) HCWs, respectively, and 1 and 8 months after the third dose in 17/486 (3.5%) and 152/486 (31.3%) HCWs, respectively. A comparison of immune responses 1 month after the third dose in vaccinated HCWs without a BI or with a BI in the next 7 months did not detect any statistically significant differences in the TAbs-WT (median (IQR): 16,611.0 (13,011.0) U/mL vs. 17,572.5 (14,501.0) U/mL, p = 0.529) and NAbs-WT (median (IQR): 96.5% (1.7) vs. 96.7% (1.9), p = 0.555). After infection, HCWs with a BI had significantly increased TAbs-WT levels at all time points compared to healthy HCWs. The findings of the present study indicate that antibody levels after three doses of the BNT162b2 vaccine are not directly associated with the possibility of a BI.