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.

Systemic Adverse Effects Induced by the BNT162b2 Vaccine Are Associated with Higher Antibody Titers from 3 to 6 Months after Vaccination

“…Not only high Ab responses against SARS-CoV-2 spike protein but also systemic adverse effects induced by the BNT162b2 vaccine were reported to be more common among participants with preexisting immunity due to COVID-19 infection [ 10 ], suggesting that some systemic adverse effects are induced as a more vigorous response to the SARS-CoV-2 spike protein itself produced by the BNT162b2 vaccine. Previous publications reported that adverse effects induced by the BNT162b2 vaccine had no correlation or only low correlation with Ab titers detected immediately after vaccination [ 5 , 6 , 7 , 8 ]. However, to evaluate the long-term effects of vaccination, research should consider Ab titers several months after vaccination and not only the peak level of Ab titers.…”

“…If the maximum vaccine efficacy, including antibody (Ab) responses, is guaranteed, most people will accept a certain severity of vaccination-related adverse effects [ 2 ]. Although several reports concluded that there is no correlation or only low correlation between adverse effects and the Ab titers detected immediately after vaccination [ 5 , 6 , 7 , 8 ], a correlation is expected between adverse effects and the Ab titers detected several months after vaccination [ 9 ]. Antibody titers alone do not correlate perfectly with protection because the benefits of mRNA vaccines include not only B-cell/humoral responses but also T-cell/cell-mediated immunity.…”

Short-Term Adverse Events and Antibody Response to the BNT162b2 SARS-CoV-2 Vaccine in 4156 Health Care Professionals

“…Among the factors influencing the IgG response 10 days after the second vaccine dose, we observed that adverse events are significantly correlated with the antibody titer, as previously suggested by a smaller study on healthy subjects [ 19 ]. Other studies failed to identify a correlation between adverse events and the IgG titers one month following the BNT162b2 vaccination, but the same authors identified sex and body weight as predictors of the incidence of adverse events [ 20 ]. Our data confirm that female gender and younger age are significantly associated with adverse events, and this may reflect the more efficacious immune response observed in women for SARS [ 21 ] and other vaccines [ 22 ], particularly at a younger age.…”

Fever after Vaccination against SARS-CoV-2 with mRNA-Based Vaccine Associated with Higher Antibody Levels during 6 Months Follow-Up

“…By 21 January 2022, 60.3% of the world’s population had received at least one COVID-19 vaccine, making it the world’s largest vaccination campaign ever [ 5 ]. However, potential relationship between vaccine-related ARs and immunogenicity has been strongly disputed, poorly investigated and the currently available evidence is contradictory [ 6 , 7 ]. The main objective of the present study was to elucidate the long-term effect of such ARs on antibody production in healthcare workers with and without prior COVID-19 infection.…”