mRNA-based seasonal influenza vaccines: an overview of immunogenicity, efficacy, and safety
TL;DR
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.
Abstract
Available seasonal influenza vaccines, most of which are still produced in eggs, have several limitations. Messenger RNA (mRNA) technology has emerged as a transformative approach capable of overcoming some of these shortcomings. This overview synthesizes clinical trials evaluating the immunogenicity, efficacy, and safety of standalone and combination mRNA influenza vaccines. Moderna’s mRNA-1010 (now approved in the United States) and Pfizer’s modified-nucleoside RNA candidate (modRNA) represent the most advanced standalone platforms, while Moderna’s combination influenza and COVID-19 vaccine, mRNA-1083, was recently granted European authorization. Following iterative platform optimization, these vaccines induce robust humoral and cell-mediated responses, especially against influenza A strains, characterized by extended germinal center reactions, continuous somatic hypermutation, enhanced Fc-mediated effector functions, and strong T helper 1 engagement. 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.