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

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.