mRNA Expands Beyond COVID-19 Vaccines: FDA Approves First Seasonal Influenza mRNA Vaccine

For the first time since the COVID-19 pandemic, mRNA technology has formally entered routine seasonal influenza vaccination in the United States. The U.S. Food and Drug Administration (FDA) approved Moderna’s mFLUSIVA to prevent disease caused by the influenza A and B viruses covered by the vaccine in adults aged 50 and older. It is also the first seasonal influenza mRNA vaccine approved for marketing in the United States.

mFLUSIVA, developed under the code name mRNA-1010, uses lipid nanoparticles to encapsulate three mRNA sequences that instruct human cells to produce hemagglutinin antigens from A/H1N1, A/H3N2, and B/Victoria-lineage viruses. Compared with traditional manufacturing processes that rely on chicken eggs or cell culture, the mRNA platform could theoretically make it easier to replace antigen sequences quickly. However, actual protection still depends on how well the vaccine strains match the viruses circulating during a given season.

The FDA used two different approval pathways. The vaccine received traditional approval for people aged 50 to 64, based primarily on a Phase 3 trial involving approximately 40,800 participants. Participants were randomly assigned to receive mFLUSIVA or a standard-dose influenza vaccine. The results showed approximately 27% fewer PCR-confirmed cases of influenza-like illness meeting the trial definition in the mFLUSIVA group. This represents a difference relative to the comparator vaccine and cannot be interpreted as a 27-percentage-point reduction in recipients’ absolute risk of infection.

For people aged 65 and older, the vaccine received accelerated approval based on a different body of evidence. The FDA primarily used antibody responses from a smaller study, compared with an existing high-dose influenza vaccine, as a surrogate endpoint that may predict clinical benefit. This is not equivalent to directly demonstrating a reduction of the same magnitude in influenza cases. Moderna is required to conduct a postmarketing confirmatory study, expected to span two influenza seasons, to verify the vaccine’s actual protective benefit in older adults.

Existing data have not identified major safety concerns, but transient reactions such as injection-site pain, fever, headache, fatigue, and muscle aches occurred more often among mFLUSIVA recipients. Because influenza vaccines must be updated every year to reflect changes in viral strains, postapproval safety monitoring, effectiveness across different influenza seasons, and comparisons with high-dose or adjuvanted vaccines will do more than the results of a single-year trial to determine its clinical role.

Moderna said it expects to supply mFLUSIVA through selected channels in the United States during the 2026–2027 influenza season, and the vaccine is under regulatory review in Europe, Canada, and Australia. The approval adds another manufacturing platform for influenza vaccines and opens a new market for Moderna, which is highly dependent on revenue from COVID-19 vaccines. However, whether it can translate into faster annual supply, more consistent protection, and widespread uptake remains to be answered by subsequent research and real-world data.