Adverse Effects and Antibody Titers in Response to the BNT162b2 mRNA COVID-19 Vaccine in a Prospective Study of Healthcare Workers

Abstract

Background: The relationship between postvaccination symptoms and strength of antibody responses is unclear. The goal of this study was to determine whether adverse effects caused by vaccination with the Pfizer/BioNTech BNT162b2 vaccine are associated with the magnitude of vaccine-induced antibody levels.

Methods: We conducted a single-center, observational cohort study consisting of generally healthy adult participants that were not severely immunocompromised, had no history of coronavirus disease 2019, and were seronegative for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein before vaccination. Severity of vaccine-associated symptoms was obtained through participant-completed questionnaires. Testing for immunoglobulin G antibodies against SARS-CoV-2 spike protein and receptor-binding domain was conducted using microsphere-based multiplex immunoassays performed on serum samples collected at monthly visits. Neutralizing antibody titers were determined by microneutralization assays.

Results: Two hundred six participants were evaluated (69.4% female, median age 41.5 years old). We found no correlation between vaccine-associated symptom severity scores and vaccine-induced antibody titers 1 month after vaccination. We also observed that (1) postvaccination symptoms were inversely correlated with age and weight and more common in women, (2) systemic symptoms were more frequent after the second vaccination, (3) high symptom scores after first vaccination were predictive of high symptom scores after second vaccination, and (4) older age was associated with lower titers.

Conclusions: Lack of postvaccination symptoms after receipt of the BNT162b2 vaccine does not equate to lack of vaccine-induced antibodies 1 month after vaccination.

Keywords: COVID-19; SARS-CoV-2; adverse effects; antibody titer; mRNA vaccine.

Figure 1.

Symptom severity after the first vaccination with BNT162b2 correlates with severity of symptoms after the second vaccination. (A) Total symptom severity scores (range 0–48), (B) duration of symptoms, (C) systemic symptom severity scores (range 0–32), and (D) local symptom severity scores (range 0–12) after the first (orange) and second (blue) vaccinations. (E) Correlation of vaccination 1 and vaccination 2 symptom scores. (F) Percentage of subjects categorized as having low (≤10, teal) or high (>10, red) total symptom scores after vaccination 1 that exhibited symptom scores of 0–2, 3–4, 5–7, 8–10, or >10 after vaccination 2. N = 206 for all panels. ∗∗∗∗P < .0001. NS = not significant, significance assessed by Wilcoxon signed-rank test for A–D and by Spearman correlation analysis for E. Bars represent mean and standard deviation in A–D.

Figure 2.

Younger age, female sex, and lower weight are associated with higher symptom severity. Total symptom severity scores after vaccination 1 (orange) and vaccination 2 (blue) graphed against age (A and B), sex (C and D), and weight (E and F). Correlations were assessed by Spearman rank analysis for age and weight. Mann-Whitney analysis was used to assess for significance between males and females. N = 206 for all panels. ∗P < .05; ∗∗P < .01; ∗∗∗P < .001. NS is defined as not significant. Bars represent median and interquartile range in C and D.

Figure 3.

Age, but neither sex nor weight, correlates with BNT162b2-induced anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody titers. Samples collected ~1 month after participants received the second vaccine dose were tested for antibodies against SARS-CoV-2 spike protein (green) and receptor-binding domain ([RBD] purple) and plotted against age (A–C), sex (D–F), and weight (G–I). Antibody reactivity against SARS-CoV-2 spike protein in samples diluted 1:400 was assessed in 206 subjects and reported as mean fluorescence intensity (MFI). Endpoint dilution titers were measured in a subset of 101 subjects for both antispike immunoglobulin (Ig)G and anti-RBD IgG. Correlations were assessed by Spearman rank analysis for age and weight, and Mann Whitney analysis was used to assess for significance between males and females. N = 206 for MFI values; n = 101 for antibody titers. ∗P < .05. Bars indicate median and interquartile range (D) or geometric mean (E and F). Titers recorded as >32000 are plotted as 64000.

Figure 4.

Severity of symptoms after vaccination correlates with neither vaccine-induced antispike immunoglobulin (Ig)G reactivity nor with titers of antispike and anti-receptor-binding domain (RBD) IgG antibodies. Samples collected ~1 month (mean 36.8 days for A-B and 33.9 days for C-H) after participants received the second vaccine dose of BNT162b2 were tested for antibodies against SARS-CoV-2 spike and RBD proteins using the Luminex microsphere-based multiplex immunoassay. (A and B) Levels of antispike IgG antibodies, as measured by mean fluorescence intensity (MFI), were plotted against symptom scores reported after first (orange) and second (blue) vaccination (N = 206). (C and D) Titers of antispike IgG antibodies, (E and F) anti-RBD IgG antibodies, and (G and H) neutralizing antibodies were plotted against symptom scores reported after first and second vaccination (n = 101). Bars indicate mean and standard deviation (A and B) or geometric mean (C–F). Titers recorded as >32000 are plotted as 64000. Assessments for correlations were conducted by both Kruskal-Wallis analysis with subjects binned into categories of symptom score ranges and by Spearman rank analysis evaluating antibody levels against symptom scores as a continuous variable. All showed no significant correlations.