Antibody titres decline 3-month post-vaccination with BNT162b2

Abstract

Several studies reported on the humoral response in subjects having received the BNT162b2 mRNA COVID-19 vaccine. However, data on the kinetics of antibodies 3 months post-vaccination are currently lacking and are important to drive the future vaccination strategy. The CRO-VAX HCP study is an ongoing multicentre, prospective and interventional study designed to assess the antibody response in a population of healthcare professionals who had received two doses of the BNT162b2 mRNA COVID-19 vaccine. Two hundred individuals underwent a blood drawn within 2 days before the first vaccine dose. One-hundred and forty-two persons (71%) were categorized as seronegative at baseline while 58 (29%) were seropositive. Samples were then collected after 14, 28, 42, 56, and 90 days. Antibodies against the SARS-CoV-2 nucleocapsid and the receptor binding domain of the S1 subunit of the spike protein were measured in all individuals at different time points. Using a one-compartment kinetics model, the time to maximum concentration was estimated at 36 ± 3 days after the first dose and the estimated half-life of antibodies was 55 days (95% CI: 37-107 days) in seronegative participants. In seropositive participants, the time to maximum concentration was estimated at 24 ± 4 days and the estimated half-life was 80 days (95% CI: 46-303 days). The antibody response was higher in seropositive compared to seronegative participants. In both seropositive and seronegative subjects, a significant antibody decline was observed at 3 months compared to the peak response. Nevertheless, the humoral response remained robust in all participants.

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

Figure 1.

Evolution of SARS-CoV-2 nucleocapsid antibodies (COI) in seronegative (blue) and seropositive individuals (red) according to the time since the first vaccine dose administration. Means with 95% confidence intervals (log₁₀) are shown. The black dotted line corresponds to the positivity cut-off (i.e. 0.165 COI). ns = non significant differences between timepoints (P < 0.05).

Figure 2.

Evolution of SARS-CoV-2 spike antibodies (U/mL) in seronegative (blue) and seropositive individuals (red) according to the time since the first vaccine dose administration. (A) Means with 95% confidence intervals are shown. 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. Forty-six samples were rounded to 25,000 U/mL out of 1195 (3.8%). Results < 0.4 U/mL (limit of quantification) were rounded to 0.4. ^$ = statistically different from all other groups (i.e. P < 0.0001). (B) Kinetic models of the humoral response based on a one-compartment model. A zoom of the seronegative population is presented in the right-upper part of the figure. Means with one standard deviation are shown.