Waning of IgG, Total and Neutralizing Antibodies 6 Months Post-Vaccination with BNT162b2 in Healthcare Workers

Abstract

Data about the long-term duration of antibodies after SARS-CoV-2 vaccination are still scarce and are important to design vaccination strategies. In this study, 231 healthcare professionals received the two-dose regimen of BNT162b2. Of these, 158 were seronegative and 73 were seropositive at baseline. Samples were collected at several time points. The neutralizing antibodies (NAbs) and antibodies against the nucleocapsid and the spike protein of SARS-CoV-2 were measured. At day 180, a significant antibody decline was observed in seronegative (-55.4% with total antibody assay; -89.6% with IgG assay) and seropositive individuals (-74.8% with total antibody assay; -79.4% with IgG assay). The estimated half-life of IgG from the peak humoral response was 21 days (95% CI: 13-65) in seronegative and 53 days (95% CI: 40-79) in seropositive individuals. The estimated half-life of total antibodies was longer and ranged from 68 days (95% CI: 54-90) to 114 days (95% CI: 87-167) in seropositive and seronegative individuals, respectively. The decline of NAbs was more pronounced (-98.6%) and around 45% of the subjects tested were negative at day 180. Whether this decrease correlates with an equivalent drop in the clinical effectiveness against the virus would require appropriate clinical studies.

Keywords: BNT162b2; COVID-19; SARS-CoV-2; antibody response; mRNA vaccine; neutralizing antibodies.

Figure 1

(Previous page). Evolution of SARS-CoV-2 spike antibodies (U/mL) in seronegative (A and C for total antibodies and IgG, respectively) and seropositive individuals (B and D for total antibodies and IgG, respectively) according to the time since the first vaccine dose administration. Means with 95% confidence intervals are shown. (A,B) Using the total antibody assay, an automatic dilution of 1/100 at >250 U/mL was performed by the analyzer to extend the measurement domain up to 25,000 U/mL. A total of 46 samples were rounded to 25,000 U/mL out of 1337 (3.4%). Results < 0.4 U/mL (limit of quantification) were rounded to 0.4. (C,D) Using the IgG assay, an automatic dilution of 1/4 at > 40,000 AU/mL was manually performed to extend the measurement domain to 160,000 AU/mL. Results < 21 AU/mL (limit of quantification) were rounded to 21. $, statistically different from all other groups (i.e., p < 0.0001); #, statistically different from all other groups (i.e., p < 0.0001) except between time points 14 and 180.

Figure 2

(Previous page). Kinetics models of (A) total antibodies and (B) IgG serological response. A zoom of the seronegative population is presented in the right-upper part of the Figure A. Means plus/minus standard deviation are shown at the different timepoints. The magnitude of the response depends on the analytical kit and the difference between COVID-19 naïve and seropositive individuals is less marked with IgG than with total antibodies.

Figure 3

Evolution of SARS-CoV-2 NAbs in seronegative (blue, n = 42) and seropositive individuals (red, n = 18) at baseline and 1 month, 3 months and 6 months after the first vaccine shot.