Against the Standard Flu Shot, an mRNA Vaccine Came Out Ahead in Younger Adults

CATEGORY: IMMUNE HEALTH

When mRNA flu vaccines were shown to protect adults 50 and older better than conventional shots, one question hung in the air: what about everyone younger? A trial of 18,476 adults aged 18 to 64 supplies the answer. Pfizer’s mRNA vaccine led to 34.5% fewer lab-confirmed flu illnesses than a standard shot, 57 cases against 87, across a single flu season.¹

Every Participant Got a Real Vaccine

There was no placebo arm. Each person received either the mRNA shot or a licensed inactivated vaccine, the familiar kind grown the slow way, and a random draw nobody could influence settled which. That design raises the bar. Beating a vaccine that already works is harder than beating salt water, and this trial was built to show superiority, not just a tie. It cleared that mark, though with a wide margin of uncertainty: the true advantage could plausibly sit anywhere from 7% to 54%. Sites spanned the United States, South Africa, and the Philippines in the 2022-2023 season, and a flu case only counted if a laboratory confirmed the virus at least two weeks after vaccination.

The Trade: Fewer Infections, Rougher Two Days

The stronger protection wasn’t free. Injection-site reactions hit 70.1% of mRNA recipients versus 43.1% with the standard shot, and fever hit 5.6% versus 1.7%. Most of it was mild or moderate and brief. Serious adverse events ran about 1% in both groups, and no cases of myocarditis or pericarditis, the heart inflammation watched for with mRNA technology, were confirmed in either arm.

The Gaps a Single Season Left

Every confirmed case that season was influenza A. No one caught influenza B, so the vaccine’s performance against B strains is simply unknown. Adults 65 and older, children, pregnant women, and people with weakened immune systems weren’t enrolled, and Pfizer’s shot remains investigational. The older-adult half of the picture is further along: a Moderna mRNA flu vaccine won FDA approval in August 2026 for adults 50 and up, after its own 40,805-person trial counted 26.6% fewer confirmed cases than a standard vaccine.² Two different companies, two different trials, one direction.

Key Takeaways

• Head to head against a standard flu shot, Pfizer’s mRNA vaccine meant about a third fewer lab-confirmed flu cases in adults 18 to 64, at 57 cases versus 87.
• The cost was comfort: sore arms and fever were notably more common, while serious adverse events stayed equal and rare.
• One season, no influenza B cases, and no one over 64 enrolled, so the result is strongest for healthy younger adults against influenza A.
• It lines up with the separate Moderna trial in adults 50 and older, which led to that vaccine’s approval in 2026.

References

1. Fitz-Patrick D, McVinnie DS, Jackson LA, et al. Efficacy, Immunogenicity, and Safety of Modified mRNA Influenza Vaccine. New England Journal of Medicine. 2025;393:2001–2011. link
2. Leroux-Roels I, et al. Efficacy and Safety of an mRNA Seasonal Influenza Vaccine in Adults. New England Journal of Medicine. 2026;394(18):1803–1813. link