Safety of pairwise co-administration of influenza, PCV20, and RZV vaccines in adults aged ≥50 years: a post-marketing surveillance study using VAERS data

Background With the accelerating global aging of the population, the disease burden of influenza, pneumococcal disease, and herpes zoster among adults aged ≥50 years is increasing. Although guidelines such as those from the Advisory Committee on Immunization Practices (ACIP) recommend that influenza, 20-valent pneumococcal conjugate vaccine (PCV20), and recombinant zoster vaccine (RZV) vaccines can be co-administered, real-world post-marketing safety data on co-administration remain limited. Methods By analyzing 25,697 reports from the Vaccine Adverse Event Reporting System (VAERS), we compared adverse event profiles between three co-administration strategies (INF+PCV20, RZV+PCV20, INF+RZV) and their respective single-vaccine comparator groups. We jointly employed four disproportionality analysis algorithms (Empirical Bayes Geometric Mean (EBGM), Bayesian Confidence Propagation Neural Network (BCPNN), Proportional Reporting Ratio (PRR), and Reporting Odds Ratio (ROR)) for signal detection and further performed disease history network analysis of serious adverse event cases. Results Co-administration groups (n = 260–348) exhibited serious adverse event rates of 3.7%–5.5%, comparable to or lower than those in single-vaccine groups (3.5%–6.6%), with no deaths reported. The majority of adverse events were mild local reactions, with injection-site erythema occurring in 13.8%–16.6% of cases. Disease history network analysis of serious adverse event cases in co-administration groups demonstrated that cardiovascular diseases and metabolic disorders formed the central hubs of the disease co-occurrence networks. Conclusion These findings indicate that, compared with single-dose administration, pairwise co-administration of INF, PCV20, and RZV in this dataset was associated with only transient reactogenicity and no evidence of excess serious adverse events.