Table 1_mRNA-based seasonal influenza vaccines: an overview of immunogenicity, efficacy, and safety.docx

In phase III relative efficacy trials, an optimized mRNA-1010 formulation achieved superiority over standard-dose vaccines with a relative efficacy of 26.6% (95% CI: 16.7%, 35.4%) in adults aged ≥50 years. Pfizer’s first-generation quadrivalent modRNA candidate showed 34.5% (95% CI: 7.4%, 53.9%) relative efficacy against a standard-dose comparator in younger adults aged 18–64 years, but failed to demonstrate non-inferiority in older adults (≥65 years), showing a relative efficacy of −5.8% (95% CI: −47.2%, 23.8%).

However, whether mRNA platforms offer incremental benefits over enhanced formulations (such as high-dose, adjuvanted, or recombinant vaccines), which are the preferred options in some countries for older adults, remains to be established. The safety profile aligns with licensed COVID-19 mRNA vaccines; although reactogenicity is higher than with conventional vaccines, adverse reactions are predominantly mild-to-moderate and transient.

Operationally, transitioning to single-dose pre-filled syringes alongside expanding refrigerated stability data significantly mitigates historical cold-chain bottlenecks. However, while standalone and combination mRNA platforms represent a major technological advance, real-world implementation challenges may affect their broader global health impact.</p>