CATEGORY: IMMUNE HEALTH
An mRNA-based flu vaccine produced 26.6% fewer confirmed flu illnesses than a standard flu shot in a randomized trial of 40,805 adults aged 50 and older—411 cases (2.0%) among mRNA recipients versus 557 cases (2.8%) with the standard vaccine—across the 2024–2025 flu season, according to results published in the New England Journal of Medicine.1 In August 2026, the FDA approved the vaccine, called mFlusiva, for adults 50 and older, making it the first mRNA vaccine for influenza to reach the market—which means the shot this trial tested is now something a pharmacist can actually draw up.
From Chicken Eggs to Genetic Instructions
Most flu vaccines are still made the way they have been for decades: by growing the virus in chicken eggs, a process that takes months and locks in the choice of strains long before flu season arrives. mRNA vaccines work differently—instead of delivering pieces of a grown virus, they deliver a short-lived genetic instruction sheet that teaches your own cells to build one harmless flu protein, which the immune system then learns to recognize. Because no eggs and no live virus are involved, production is faster, which in principle lets vaccine makers wait longer before committing to the season’s strains. The trial’s authors noted the platform’s promise of improved protection in older adults as a reason to run the comparison.
Forty Thousand Adults, One Flu Season, Twice-Weekly Check-Ins
The trial, funded by Moderna and Blackstone Life Sciences, assigned each of its 40,805 participants by chance—the design that lets the result be credited to the vaccine itself—to receive either the mRNA vaccine or a licensed standard-dose flu shot, across 11 countries. Surveillance was active rather than passive: participants filled in symptom diaries twice a week, and anyone with flu-like symptoms had a nose swab within 72 hours, tested by RT-PCR, a laboratory method that detects the virus’s genetic material. A case only counted if the virus was confirmed, starting two weeks after vaccination and running to the season’s end.
Eight Fewer Cases in Every Thousand
Confirmed flu-like illness struck 2.0% of the mRNA group versus 2.8% of the standard-shot group—in round numbers, 20 out of every 1,000 people versus 28 out of every 1,000. That works out to 26.6% fewer cases relative to an already-working vaccine, with a confidence range of 16.7% to 35.4%. The trial was built to clear two prespecified bars in order: first showing the new vaccine was no worse than the standard shot, then showing it was better. It cleared both. Among the 19,260 participants aged 65 and older, the advantage held at 27.4%.
The Sore Arms, and the Question the Trial Didn’t Ask
The stronger immune response came at a cost in comfort: 65.8% of mRNA recipients reported injection-site pain versus 29.8% with the standard shot, and fatigue, headache and muscle aches were all more common. Serious adverse events were similar between groups—2.2% versus 1.9%—and no cases of myocarditis or pericarditis, the heart-inflammation conditions watched for with mRNA vaccines, were identified in the 42-day monitoring window. One question the trial left open, and the authors say so plainly: the comparator was a standard-dose shot, while several countries already recommend enhanced flu vaccines—high-dose or immune-boosted versions—for adults 65 and older. In a 2014 randomized trial of 31,989 older adults, the high-dose vaccine itself beat the standard dose by about 24%2—a similar margin to the mRNA result—and the head-to-head test between mRNA and those enhanced shots has not been run. The FDA has also required a follow-up study of the new vaccine’s safety and effectiveness after launch.
Key Takeaways
- In a 40,805-adult randomized trial over the 2024–2025 season, an mRNA flu vaccine produced 26.6% fewer lab-confirmed flu illnesses than a standard-dose shot—20 versus 28 cases per 1,000 people.
- The advantage was just as large among adults 65 and older, at 27.4% in the trial’s 19,260 participants in that age group.
- Temporary side effects such as arm pain, fatigue and headache were notably more common with the mRNA vaccine, while serious adverse events were similar between groups.
- The trial compared the mRNA vaccine only with standard-dose shots—not with the high-dose or immune-boosted flu vaccines many countries already recommend for adults 65 and older, a comparison that has not yet been tested.