Will the mRNA flu shot work better than a regular seasonal one? What the science says

On 5 August, the U.S. Food and Drug Administration (FDA) approved Moderna's mRNA-based flu vaccine, mFLUSIVA, for adults aged 50–64, and gave accelerated approval for those aged 65 and older. The vaccine is expected to be available within weeks for the 2026–27 flu season in the United States. This marks a pivotal moment in flu vaccination strategies, as mFLUSIVA represents the first mRNA-based flu vaccine to receive such approval in the country. Moderna's mFLUSIVA uses an mRNA platform that enables rapid reformulation to match circulating influenza strains, according to researchers. This capability addresses a longstanding challenge in vaccine development, keeping up with evolving viral mutations. The vaccine is currently under review by regulatory bodies in the European Union, Canada, and Australia. In Europe, Moderna's combined seasonal influenza and COVID-19 mRNA vaccine, mCombriax, has already received approval. Clinical trials involving more than 40,000 adults demonstrated that 2% of individuals receiving mFLUSIVA developed laboratory-confirmed flu cases, compared to 2.8% among those who received a standard non-mRNA vaccine. These results suggest that mFLUSIVA may offer improved protection against influenza. The study evaluated antigens from the three 2024–25 strains recommended by the World Health Organization for the Northern Hemisphere influenza season. Raffael Nachbagauer, vice-president of infectious-disease research at Moderna, noted that the key questions regarding immunogenicity, efficacy, and safety have been resolved, enabling the licensure of mFLUSIVA. However, further research is needed to assess its performance in real-world settings. Moderna has committed to conducting a phase IV trial to evaluate the vaccine's efficacy in people aged 65 and older, comparing it with an enhanced vaccine. The mechanism of action of mFLUSIVA involves delivering mRNA molecules encoding the flu virus's hemagglutinin surface protein, encapsulated in lipid nanoparticles. Once inside cells, these mRNA strands are translated into hemagglutinin proteins, prompting the immune system to produce antibodies. Clinical studies revealed that mFLUSIVA resulted in a 26.6% relative reduction in confirmed flu cases compared to a standard influenza vaccine. The study focused on antigens from the 2024–25 strains, highlighting the vaccine's potential to target current viral threats. Adverse effects associated with mFLUSIVA were generally mild to moderate. Common side effects included injection-site pain, fatigue, and headaches. These side effects occurred more frequently in individuals receiving the mRNA vaccine compared to those receiving a standard-dose comparator. Injection-site pain was reported more than twice as often with mFLUSIVA as with the standard-dose vaccine. In addition to its effectiveness, mFLUSIVA has shown promise in enhancing immune responses in older adults. A separate study comparing mFLUSIVA with licensed comparators found that a single dose of the mRNA vaccine generated a stronger antibody response than standard or high-dose flu shots. This finding supports the accelerated approval for the 65-and-older demographic, as it indicates that mFLUSIVA may provide better protection for vulnerable populations. Federico Martinón-Torres, head of pediatrics at the University Clinical Hospital of Santiago de Compostela, emphasized that even a relative improvement over a standard-dose vaccine is clinically meaningful. As the vaccine moves closer to widespread use, ongoing monitoring and additional trials will be essential to ensure its long-term safety and efficacy. The rollout of mFLUSIVA could represent a significant shift in flu prevention strategies, offering a new tool in the fight against seasonal influenza.