Decline of antibody titres 3 months after two doses of BNT162b2 in non-immunocompromised adults

Abstract

Objective: To assess the antibody response in non-immunocompromised adults after two doses of BNT162b2.

Methods: Prospective, single-centre observational study in non-immunocompromised adults aged 18 years or more who received two doses of BNT162b2. The study contemplates analyses of serum samples collected 1.5, 3, 6, 9 and 12 months after the second dose of BNT162b2; results of the 1.5- and 3-month time-points are presented in this report. Antibodies against the receptor binding domain of the S1 subunit of the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (anti-RBD antibodies) were measured using a commercial quantitative immunoassay. A threshold of 4160 AU/mL (corresponding to an ID₅₀ of 1:250) was used as surrogate marker for serum neutralizing activity.

Results: Of 273 hospital workers who received two doses of BNT162b2, 260 (95%) agreed to participate in the study; 2/260 (0.8%) were excluded because of immunocompromised conditions. At the time of this report, 230/258 (89%) participants (mean age 46.0 years (SD 11.4 years); 143/230 (62%) female; 87/230 (38%) male) had completed 3 months of follow up after the second dose of BNT162b2. Thirty-six (16%) of the 230 had documented mild SARS-CoV-2 infection before receiving the first dose of BNT162b2. Median (interquartile range (IQR)) anti-RBD titres 1.5 months after vaccination were 9356 (5844-16 876) AU/mL; 3 months after vaccination, median anti-RBD titres had declined to 3952 (2190-8561) AU/mL (p < 0.001). Of 199/230 (86.5%) participants who had anti-RBD titres above 4160 AU/mL 1.5 months after the second dose of BNT162b2, only 95/230 (41%) maintained anti-RBD titres above this level 3 months after vaccination (p < 0.001).

Conclusions: The decline of anti-RBD antibodies 3 months after the second dose of BNT162b2 is of concern because it raises the possibility of a short-lived humoral immunity after vaccination. Booster doses of BNT162b2 might be required to maintain high titres of anti-RBD antibodies over time.

Keywords: BNT162b2; COVID-19; Immunogenicity; SARS-CoV-2; Vaccine.