Decreased humoral immune response to BNT162b2 Covid-19 vaccine over 6 months
Study population and serological assays
This study involved a prospective cohort of healthcare workers who had received the BNT162b2 vaccine and had undergone at least one serological test after receiving the second dose of the vaccine. During the study period (December 19, 2020 to July 9, 2021), participants were followed monthly for 6 months after receiving the second dose. PCR refers to the polymerase chain reaction and SARS-CoV-2 severe acute respiratory syndrome coronavirus 2.
The study was conducted from December 19, 2020 to July 9, 2021. Of the 12,603 vaccinated health workers eligible for the study, 4,868 were recruited to participate in the study (Figure 1). During the study period, 20 participants had a breakthrough SARS-CoV-2 infection (defined as a positive PCR result for SARS-CoV-2) and 5 had a positive anti-N result. A total of 14,736 IgG assays and 4,521 neutralizing antibody assays were performed. The number of people who underwent repeated IgG tests and neutralizing antibody tests are shown in Figure 1. IgG levels were assessed at least once for all study participants during the 6-month follow-up and at least twice for 2631 participants (54.0%). The neutralizing antibody subgroup included 1269 participants (26.1%) who underwent at least one neutralizing antibody test; 955 of these participants (75.3%) were tested at least twice. Data on age and gender were available for all study participants. Overall, 3,808 participants (78.2%) responded to the computerized questionnaire and were included in the mixed model analysis.
Demographic characteristics and data on coexisting conditions in study participants are provided in Table S1, both in the general population and in the neutralizing antibody subgroup. The mean (± SD) age of the participants was 46.9 ± 13.7 years in the general population and 52.7 ± 14.2 years in the neutralizing antibody subgroup. The distributions of demographic characteristics and coexistence conditions among participants by study period and IgG and neutralizing antibody dosages are provided in Tables S4 and S5.
Kinetics of SARS-CoV-2 antibody after receiving the second dose of vaccine
Panels A and B show the geometric mean titers (GMT) of IgG and neutralizing antibodies, respectively, in the entire study population, and panels C through F show GMTs by age group and sex. Antibodies were tested monthly for seven periods after receiving the second dose of vaccine. Dots represent individual observed serum samples. The dotted line in each panel indicates the threshold for diagnostic positivity. Bars indicate 95% confidence intervals. RBD refers to the receptor binding domain.
The antibody response and kinetics were assessed for 6 months after receiving the second dose of vaccine (Figures 2A and 2B and S1 and Table S6). The highest titers after receiving the second vaccine dose (peak) were seen on days 4-30, which was defined as the peak period. The expected geometric mean titer (GMT) for IgG for the peak period, expressed as a sample / cutoff ratio, was 29.3 (95% confidence interval [CI], 28.7 to 29.8). A substantial reduction in the IgG level each month, which resulted in an 18.3-fold decrease after 6 months, was observed. Neutralizing antibody titers also decreased significantly, with a 3.9-fold decrease from the peak at the end of study period 2, but the decrease from the start of period 3 was significantly. slower, with an overall decrease by a factor of 1.2 during periods 3 to 6. The GMT of the neutralizing antibody, expressed as 50% neutralization titer, was 557.1 (95% CI, 510 , 8 to 607.7) during the peak period and decreased to 119.4 (95% CI, 112.0 to 127.3) during the period 6.
Differential caries by age and sex
The kinetics of IgG and neutralizing antibodies showed differences in immunogenicity by age group and sex (Figure 2C to 2F). The rate of IgG decay in all age and sex defined subgroups was constant throughout the 6 month period, while neutralization was significantly reduced up to period 3, followed by slower decrease thereafter. Participants aged 65 or older had lower levels of IgG and neutralizing antibodies than those aged 18 to under 45 during the peak period and also had a larger decrease, down to about 3 month (end of period 2), the neutralization rate. antibody titer (Figure 2C and 2D, and see additional results, sections S1 and S2).
Peak and end-of-study antibody titers predictors
During the peak and end periods of the study, significantly lower IgG titers were associated with older age, males, the presence of two or more coexisting conditions (i.e. -d. hypertension, diabetes, dyslipidemia or heart, lung, kidney or liver disease), the presence of autoimmune disease and the presence of immunosuppression. Significantly lower neutralizing antibody titers were associated with advanced age, male sex, and the presence of immunosuppression in both time periods, and significantly higher neutralizing antibody titers were associated with a BMI of 30 or more (obesity) compared to a BMI of less than 30 in both study periods. Our results show that although the titers of IgG and neutralizing antibodies were significantly lower in participants with two or more specific coexisting conditions than in those without a specific coexisting condition during the peak period, no significant difference in titers. neutralizing antibodies were observed at the end of the study. . In addition, participants with autoimmune disease had significantly lower IgG titer but no neutralizing antibody titer during peak and end of study periods than those without autoimmune disease. An age-by-sex interaction was found; the difference in which the titles of men aged 45 and over were lower than the titles of men under 45 was greater than the difference between the corresponding groups of women.
At the end of the study, the mixed model analysis showed decreases in IgG and neutralizing antibody concentrations of 38% and 42%, respectively, in people 65 years of age or older compared to participants. 18 to under 45 and 37% and 46%, respectively, among men 65 years of age or older compared to women of the same age group (Table 1). Immunosuppressed participants had decreases in IgG and neutralizing antibody concentrations of 65% and 70%, respectively, compared to participants without immunosuppression. Obese participants (those with a BMI 30) had a 31% increase in neutralizing antibody concentrations compared to non-obese participants (Table 1).
For IgG levels, the correlation between individual participants’ peak levels and their declining slopes was positive but weak (0.17; 95% CI, 0.11 to 0.24); decay rates were not strongly related to initial levels. However, for neutralizing antibodies, the correlation was strongly negative (-0.63; 95% CI, -0.70 to -0.55). After adjusting for other factors, participants with a higher baseline tended to have a decrease which was faster until about 70 days after receiving the second dose. Beyond this period, decay rates were modest and did not vary much between participants.
We used the mixed model to predict the likelihood in different subgroups of achieving a neutralizing antibody titer below the diagnostic positivity test cutoff (i.e. Table 2). In healthy women and men in all three age groups (18 to Table 2).
Correlation between IgG and neutralizing antibody levels
We assessed the correlation between IgG and neutralizing antibody levels. Although a strong correlation between IgG and neutralizing antibody titers was maintained for 6 months after receipt of the second dose of vaccine (Spearman rank correlation between 0.68 and 0.75) (Fig S2), the regression relationship between IgG and neutralizing antibody levels depended on the time elapsed since the second dose of vaccine, a result which was likely due to the difference in kinetics between IgG and d. ” neutralizing antibodies (Figure 2).