mRNA Flu Vaccine Outperforms Standard Shots in Adults Over 50
Moderna's mRNA-1010 influenza vaccine cut flu illness by 26.6% more than standard-dose vaccines in a 40,000-person phase 3 trial.
Summary
A large phase 3 trial found that Moderna's mRNA-based seasonal influenza vaccine, mRNA-1010, was superior to standard-dose licensed flu vaccines in adults aged 50 and older. The trial enrolled over 40,000 participants across multiple countries. Recipients of mRNA-1010 had a 26.6% lower rate of RT-PCR-confirmed influenza-like illness compared to those receiving the standard-dose comparator. The vaccine met all three pre-specified efficacy thresholds: noninferiority, superiority, and higher-level superiority. Side effects were more common with mRNA-1010, including injection-site pain, fatigue, headache, and muscle aches, but were mostly mild to moderate and short-lived. Serious adverse events were rare and comparable between groups.
Detailed Summary
Seasonal influenza remains a significant cause of illness and death in older adults, and existing vaccines — while helpful — leave substantial room for improvement. The emergence of mRNA vaccine technology, proven effective during the COVID-19 pandemic, has opened new possibilities for more potent and adaptable influenza vaccines.
This phase 3, double-blind, active-controlled trial called Fluent randomly assigned 40,703 adults aged 50 and older to receive either mRNA-1010, a trivalent mRNA vaccine encoding hemagglutinin from WHO-recommended influenza strains, or a licensed standard-dose comparator. The primary endpoint was relative vaccine efficacy against RT-PCR-confirmed influenza-like illness starting 14 days post-vaccination through the end of flu season.
The results were striking: influenza-like illness occurred in 2.0% of mRNA-1010 recipients versus 2.8% of comparator recipients, yielding a relative vaccine efficacy of 26.6% (95% CI: 16.7–35.4). Crucially, the trial met all three hierarchical testing criteria — noninferiority, superiority, and a higher-level superiority threshold — marking a meaningful clinical advance over current standard-dose options.
Solicited adverse reactions were more frequent with mRNA-1010, including injection-site pain (65.8% vs. 29.8%), fatigue (45.1% vs. 20.3%), headache (37.8% vs. 18.0%), and myalgia (35.4% vs. 11.6%). However, most were mild to moderate and transient. Serious adverse events were low and similar across groups (2.2% vs. 1.9%), with very few deemed vaccine-related.
For older adults — a population with higher flu-related morbidity — an mRNA-based flu vaccine offering roughly 27% improved relative efficacy could translate to meaningfully fewer hospitalizations and deaths. If regulatory approval follows, mRNA-1010 could reshape annual influenza vaccination strategies for aging populations.
Key Findings
- mRNA-1010 reduced RT-PCR-confirmed influenza-like illness by 26.6% relative to standard-dose vaccines.
- Trial met noninferiority, superiority, and higher-level superiority thresholds in hierarchical testing.
- Flu illness occurred in 2.0% of mRNA-1010 recipients vs. 2.8% of standard-dose comparator recipients.
- Side effects were more frequent with mRNA-1010 but mostly mild, moderate, and transient.
- Serious adverse events were rare and comparable between groups (2.2% vs. 1.9%).
Methodology
Phase 3, double-blind, active-controlled randomized trial (Fluent; NCT06602024) enrolling 40,703 adults aged 50+ across multiple countries. Participants received trivalent mRNA-1010 (37.5 μg total) or a licensed standard-dose influenza comparator. Primary endpoint was RT-PCR-confirmed influenza-like illness from 14 days post-vaccination through end of season, with hierarchical hypothesis testing for noninferiority and two superiority thresholds.
Study Limitations
The trial compared mRNA-1010 only to standard-dose (not high-dose or adjuvanted) comparators, which are already recommended for older adults in some guidelines, limiting head-to-head comparison with the most potent currently available options. Efficacy data are from a single influenza season and may not generalize across seasons with different circulating strains. Long-term safety follow-up beyond the trial period is not yet available.
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