N Engl J Med
mRNA flu vaccine outperforms standard shot in older adults
Clinical Takeaway: The mRNA flu vaccine could give older adults better seasonal protection than standard flu shots, though patients may need reassurance about the higher rate of short-term side effects.
Seasonal influenza continues to cause substantial illness in older adults despite widespread vaccination, and standard-dose vaccines provide only moderate protection in many seasons. Whether the mRNA approach used for COVID-19 vaccines could also improve influenza protection has been uncertain.
In this phase 3 trial, the investigational mRNA influenza vaccine mRNA-1010 outperformed licensed standard-dose influenza vaccines in adults age 50 years or older. Laboratory-confirmed influenza-like illness occurred in 2% of mRNA-1010 recipients versus 3% of those receiving standard-dose vaccines, corresponding to a relative vaccine efficacy of about 27%. The benefit met thresholds for both superiority and a stricter prespecified margin.
The trial randomized more than 40,000 adults aged 50 and older to receive trivalent mRNA-1010 or a licensed standard-dose comparator vaccine and followed participants through the influenza season. Protection was measured using PCR-confirmed influenza beginning at least 14 days after vaccination. The trial did not compare mRNA-1010 with high-dose or adjuvanted vaccines, which are typically preferred for adults age 65 years and older and other patients with higher risk for severe flu complications.
The clearest tradeoff was reactogenicity. Injection-site pain occurred in about two-thirds of mRNA-1010 recipients compared with one-third of comparator recipients. Fatigue, headache, and myalgia were also roughly two to three times as common with the mRNA vaccine. Most reactions were mild to moderate and transient, and serious adverse events were uncommon, occurring in about 2% of recipients in each arm.
The findings suggest mRNA influenza vaccines could offer a meaningful improvement in seasonal protection for older adults, a population that continues to account for much of influenza-related hospitalization and mortality. The side-effect profile, however, resembles the higher reactogenicity clinicians and patients became familiar with during mRNA COVID-19 vaccination campaigns. Setting expectations about transient systemic symptoms may be important, particularly for patients who avoided repeat COVID-19 boosters because of similar reactions.
Source: Leroux-Roels I. N Engl J Med. 2026 May 6. Efficacy and safety of an mRNA seasonal influenza vaccine in adults