Post-marketing safety surveillance of tetanus, diphtheria, and acellular pertussis (Tdap) vaccine: a disproportionality analysis of the vaccine adverse event reporting system (2015–2025)

Abstract

Background The tetanus, diphtheria, and acellular pertussis (Tdap) vaccine is routinely recommended for adolescents, adults, and pregnant individuals. Ongoing post-marketing surveillance is critical to monitor its safety profile and detect rare or unexpected adverse events (AEs) following immunization. This study aims to comprehensively analyze Tdap-related AEs reported to the Vaccine Adverse Event Reporting System (VAERS) over the past decade, with a focus on safety profiles in specific subpopulations. Methods We retrospectively analyzed US AE reports related to Tdap vaccination from VAERS for the period 2015 to May 2025. Data mining was conducted using four disproportionality algorithms: Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-Item Gamma Poisson Shrinkage (MGPS). The False Discovery Rate (FDR) was controlled at 5% to minimize false positives. Subgroup analyses focused on adolescents (aged 10–18 years), older adults (aged ≥65 years), pregnant individuals, and sex-based subgroups (males vs. non-pregnant females). Time of onset was characterized using Weibull distribution analysis. Results A total of 20,128 AE reports were identified, with 95.80% classified as non-serious. Injection site erythema, injection site swelling, and erythema were the most frequently reported positive signals. The majority of AEs (70.31%) occurred within one day of vaccination, showing an “early failure” pattern in Weibull analysis. Tdap did not exhibit any disproportionate accumulation of unexpected AEs among older adults. Among 744 pregnancy-related reports, no new or unexpected safety signals related to maternal or fetal outcomes were detected. Notably, the adolescent subgroup showed a significant signal for opisthotonus (ROR = 8.55). In non-pregnant females, bursal fluid accumulation (ROR = 21.22) and radiculitis brachial (ROR = 14.42) were disproportionately elevated, whereas no such signals were found in males. Conclusions This 10-year surveillance study revealed no unexpected signals for Tdap in the overall population, older adults, males, or pregnant women. While most reports were non-serious, the signals of radiculitis brachial in non-pregnant females generate hypotheses that require formal testing in active surveillance systems. Our findings are generally consistent with the current Tdap vaccination recommendations and highlight the importance of ongoing post-marketing surveillance.