Moderna’s first mRNA-based flu vaccine, mFlusiva (mRNA-1010), is being debated by U.S. health advisers this week as the Food and Drug Administration (FDA) weighs whether to approve the shot for adults aged 50 and older — a decision that could mark a turning point in seasonal influenza prevention.
The vaccine, if authorised, would be the first flu jab to deploy the same messenger RNA technology that proved critical during the Covid-19 pandemic. Its developers argue that the platform’s speed and flexibility could transform how the world responds to the constantly evolving influenza virus. Unlike traditional egg-based or cell-culture vaccines, which can take six months or more to manufacture, mRNA doses can be produced in roughly two to three months. That rapid turnaround could prove vital if the flu virus mutates significantly between seasons, allowing swift production of updated shots. A human-challenge trial has already shown an mRNA flu vaccine to be 100 per cent effective against symptomatic and febrile influenza, compared with 85 per cent for a conventional quadrivalent vaccine. Further research suggests mRNA vaccines may also help the immune system recognise a wider range of flu viruses, generating more flu-specific antibodies and memory B cells for potentially stronger and longer-lasting protection.
How the technology works
The mRNA platform works by instructing cells to produce a harmless piece of the virus’s surface protein, training the immune system to recognise and attack the real pathogen. It does not alter a person’s DNA. Moderna is also developing a combined Covid-19 and flu vaccine, though that remains at an earlier stage.
Regulatory hurdles and initial setbacks
Moderna’s path to the FDA advisory committee has been anything but smooth. In February 2026, the agency issued a “refusal to file” letter, initially rejecting the application for review. The decision followed an internal dispute over trial design: Dr. Vinay Prasad, then the senior FDA official serving as vaccine chief, argued that Moderna should have compared its mRNA shot to a high-dose flu vaccine recommended for older adults, rather than a standard-dose brand. The move was widely seen as an example of heightened scrutiny under Health Secretary Robert F. Kennedy Jr., who has previously expressed scepticism about mRNA technology and has reportedly cancelled investments in related research. Dr. Prasad overruled career scientists who had been prepared to review the application.
Moderna challenged the FDA’s stance, pointing out that agency staff had approved the main study’s design and citing a separate, smaller study that did compare the mRNA vaccine to a high-dose senior vaccine. That study found that mFlusiva generated flu-fighting antibodies similar to those produced by the high-dose shot. Following the company’s pushback, the FDA reversed its decision and accepted the application for review.
The key comparison study and implications for older adults
The central evidence before the advisory committee comes from a Phase 3 clinical trial involving more than 40,000 participants aged 50 and older across 11 countries during the 2024–2025 flu season. Published in the New England Journal of Medicine, the results showed that mFlusiva reduced laboratory-confirmed influenza-like illness by approximately 27 per cent compared with a standard-dose flu vaccine — a relative vaccine efficacy (rVE) of 26.6 per cent. Efficacy was consistent across strains: 29.6 per cent against influenza A/H1N1, 22.2 per cent against A/H3N2, and 29.1 per cent against B/Victoria.
For the age group most at risk — those 65 and older — the rVE was 27.4 per cent. Older adults account for an estimated 70–85 per cent of flu-related deaths and 50–70 per cent of hospitalisations in the United States. In 2018, the death rate from influenza and pneumonia among those aged 65 and older was 93.2 per 100,000, increasing with age. In the UK, individuals aged 65 and over are already offered Fluad®, an adjuvanted vaccine designed to stimulate a stronger immune response, and for the 2025–2026 season an adjuvanted inactivated influenza vaccine (aIIV) is also licensed for those aged 50 and over.
The smaller study that Moderna used to support its case measured antibody responses and indicated that its mRNA vaccine matched the immune response of a high-dose senior vaccine. However, the FDA’s initial review flagged notable gaps. The data cover only a single flu season, and there is a lack of established efficacy in very frail older adults and individuals with compromised immune systems. The agency also noted that the safety follow-up period was relatively short — six months — which may not capture rare adverse events such as myocarditis or neurological issues that have been associated with Moderna’s Covid-19 vaccine, Spikevax. Side effects were more common with mFlusiva than with the standard-dose comparator: injection-site pain (65.8 per cent vs 29.8 per cent), fatigue (45.1 per cent vs 20.3 per cent), headache (37.8 per cent vs 18.0 per cent) and myalgia (35.4 per cent vs 11.6 per cent). These were mostly mild to moderate and transient. Serious adverse events occurred in roughly 2 per cent of participants in both groups, with no significant safety concerns or imbalances in deaths.
Moderna is seeking full approval for adults aged 50 to 64 and accelerated authorisation for those 65 and older, with a commitment to conduct a post-marketing study in the older cohort. The FDA’s target decision date is 5 August 2026. The advisory committee’s recommendations are non-binding, but the agency typically follows its guidance. For now, the panel must weigh a vaccine that offers a meaningful edge over existing shots against the unanswered questions about its performance in the most vulnerable populations — and the shadow of political interference that has marked its regulatory journey.