Moderna mRNA Flu Vaccine Shows Higher Efficacy Than Standard Shot in Phase 3 Trial

Moderna’s mRNA flu vaccine provided greater protection against illness than standard flu shots in a Phase 3 clinical trial, according to results published Wednesday in the New England Journal of Medicine. The trial included more than 40,000 adults ages 50 and older who were randomly assigned to receive either the mRNA vaccine or one of four standard flu shots during the 2024–2025 flu season.

About 2 percent of participants in the mRNA group became ill, compared with 2.8 percent in the standard-shot group. The mRNA vaccine performed about 27 percent better overall. Side effects such as fatigue, headache and arm pain were more common in the mRNA group but were described as mild and short-lived.

Similar reactions are often reported after traditional flu shots.

The efficacy of seasonal flu shots varies and has been as low as 20 percent to 30 percent in some years. Messenger RNA technology is viewed as a way to improve protection because it can be updated more quickly to match circulating strains. Traditional flu vaccines take months to manufacture, requiring health officials to select strains up to 12 months before peak season.

This lead time can result in mismatches if new variants emerge. An mRNA approach would allow decisions later in the year and give manufacturers more flexibility to adjust to changes in the virus. The trial was conducted at 301 sites across 11 countries, including the United States.

Older adults are generally at higher risk of severe flu complications than younger people, with the exception of very young children.

Administration rejected Moderna’s original application earlier this year because the company had tested its vaccine against a standard flu shot rather than the higher-dose version typically recommended for adults 65 and older. The agency later allowed the company to amend its filing, splitting the application by age group.

Standard approval is being sought for adults 50 to 64, while accelerated approval is sought for those 65 and older, with a commitment to conduct an additional trial in the older group after approval. Results showed the mRNA shot performed similarly in adults 65 and older, with 1.9 percent becoming ill compared with 2.6 percent for the standard shot.

The FDA is expected to decide on the mRNA flu shot by Aug. 5. No mRNA-based flu vaccine has been approved anywhere in the world. Moderna’s flu and Covid shots use the same underlying mRNA technology. The company funded the trial and declined a request to discuss the Phase 3 results.

The Department of Health and Human Services has reduced funding for mRNA vaccine research and canceled nearly $500 million in related projects. Last May, Moderna withdrew its application for a combination flu and Covid mRNA shot after the FDA requested additional data.