Long follow-up of BNT162b2 mRNA vaccine in healthcare workers (2020-2022): A retrospective longitudinal SARS-CoV-2 serological surveillance

Abstract

SARS-CoV-2 anti-spike IgG production and protection from severe respiratory illness should be explored in greater depth after COVID-19 booster vaccination. This longitudinal observational retrospective study investigated the anti-spike IgG response elicited by the first, second and booster doses of BNT162b2 mRNA vaccine in healthcare workers (HCW) at San Martino IRCCS Policlinico Hospital (Genoa) up to the 12^th month. Sequential blood sampling was performed at T0 (prior to vaccination), T1 (21 days after the 1^st dose of vaccine), T2, T3, T4, T5, T6 (7 days and 1, 3, 6 and 9 months after the 2^nd dose, respectively), T7 and T8 (1 and 3 months after a booster dose). A SARS-CoV-2 IgG panel (Bio-Rad, Marnes-la-Coquette, France) was used to determine levels of receptor-binding domain (RBD), spike-1 (S1), spike-2 and nucleocapsid structural proteins of SARS-CoV-2. In the 51 HCWs evaluated, seroprevalence was 96% (49/51) at T1 and 100% (51/51) from T2 to T5 for RBD and S1. At T6, only one HCW was negative. T2 [RBD = 2945 (IQR:1693-5364); S1 = 1574 (IQR:833-3256) U/mL], and T7 [RBD = 8204 (IQR:4129-11,912); S1 = 4124 (IQR:2124-6326) U/mL] were characterized by the highest antibody values. Significant humoral increases in RBD and S1 were documented at T7 and T8 compared to T2 and T4, respectively (p-value < .001). Following vaccination with BNT162b2 and a booster dose in the 9^th month, naïve and healthy subjects show high antibody titers up to 12 months and a protective humoral response against COVID-19 disease lasting up to 20 months after the last booster.

Keywords: BNT162b2 vaccine; COVID-19; SARS-CoV-2; anti-spike IgG seroprevalence; healthcare workers.

Figure 1.

Temporal trends and differences of SARS-CoV-2 IgG anti-RBD (panel a) and -S1 (panel b) antibodies elicited by BNT162b2 mRNA vaccine. Serum antibody values are reported as medians (U/ml).

Figure 2.

Scatterplot of humoral immune responses to BNT162b2 mRNA vaccine in SARS-CoV-2 naïve healthcare workers. A series of SARS-CoV-2 IgG anti-RBD (panel a) and -S1 (panel b) data were plotted at different time points in the post-vaccination period. Serum antibody levels are reported as absolute values ranging from 1 to 3200 U/mL. Levels of anti-RBD and anti-S1 ≥ 3200 U/mL were reported as 3200 U/mL, the upper limit of detection. This graph does not include the results of manual dilutions.

Figure 3.

Comparison of humoral response following full vaccination with BNT162b2 at T2 and T4 and after the booster dose at T7 and T8. Average and median values, expressed as Log10 of RBD and S1 IgG 7 days after the 2^nd dose of vaccine (T2) were compared with antibody levels 1 month after a booster dose (T7), as reported in panels a and b. Similarly, average (95% CI) and median values of RBD and S1 IgG 3 months after full vaccination (T4) were compared with antibody levels 3 months after the booster dose (T8), as reported in panels c and d.