Waning Immune Humoral Response to BNT162b2 Covid-19 Vaccine over 6 Months

Abstract

Background: Despite high vaccine coverage and effectiveness, the incidence of symptomatic infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been increasing in Israel. Whether the increasing incidence of infection is due to waning immunity after the receipt of two doses of the BNT162b2 vaccine is unclear.

Methods: We conducted a 6-month longitudinal prospective study involving vaccinated health care workers who were tested monthly for the presence of anti-spike IgG and neutralizing antibodies. Linear mixed models were used to assess the dynamics of antibody levels and to determine predictors of antibody levels at 6 months.

Results: The study included 4868 participants, with 3808 being included in the linear mixed-model analyses. The level of IgG antibodies decreased at a consistent rate, whereas the neutralizing antibody level decreased rapidly for the first 3 months with a relatively slow decrease thereafter. Although IgG antibody levels were highly correlated with neutralizing antibody titers (Spearman's rank correlation between 0.68 and 0.75), the regression relationship between the IgG and neutralizing antibody levels depended on the time since receipt of the second vaccine dose. Six months after receipt of the second dose, neutralizing antibody titers were substantially lower among men than among women (ratio of means, 0.64; 95% confidence interval [CI], 0.55 to 0.75), lower among persons 65 years of age or older than among those 18 to less than 45 years of age (ratio of means, 0.58; 95% CI, 0.48 to 0.70), and lower among participants with immunosuppression than among those without immunosuppression (ratio of means, 0.30; 95% CI, 0.20 to 0.46).

Conclusions: Six months after receipt of the second dose of the BNT162b2 vaccine, humoral response was substantially decreased, especially among men, among persons 65 years of age or older, and among persons with immunosuppression.

Figure 1. Recruitment of Participants, Testing, and Follow-up.

This study involved a prospective cohort of health care workers who had received the BNT162b2 vaccine and underwent at least one serologic assay after receipt of the second dose of vaccine. During the study period (December 19, 2020, to July 9, 2021), participants were followed monthly for 6 months after receipt of the second dose. PCR denotes polymerase chain reaction, and SARS-CoV-2 severe acute respiratory syndrome coronavirus 2.

Figure 2. Distribution of Antibodies 6 Months after Receipt of Second Dose of the BNT162b2 Vaccine.

Panels A and B show the geometric mean titers (GMTs) of IgG and neutralizing antibody, respectively, in the entire study population, and Panels C through F show GMTs according to age group and sex. Antibodies were tested monthly throughout seven periods after receipt of the second dose of vaccine. Dots represent individual observed serum samples. The dashed line in each panel indicates the cutoff for diagnostic positivity. 𝙸 bars indicate 95% confidence intervals. RBD denotes receptor-binding domain.