On 5 August, the US Food and Drug Administration (FDA) granted approval to Moderna’s mRNA-based flu vaccine, mFLUSIVA, for adults aged 50–64, and accelerated approval for adults aged 65 and older. Moderna say it will be available “in a few weeks” to be rolled out for the 2026–27 flu season in the United States.

Researchers welcomed the decision, noting that the vaccine’s mRNA platform allows it to be rapidly reformulated to match circulating influenza strains. “This approval is very important and can be a great game changer” because the platform could help solve the problem of slow manufacturing, says Emanuele Montomoli, a researcher in hygiene and public health at the University of Siena, Italy.

The vaccine is also being reviewed by regulatory agencies in the European Union, Canada and Australia. A related product has already been permitted for use in Europe: in April, the European Commission approved Moderna’s combined seasonal influenza and COVID-19 mRNA vaccine mCombriax.

Tests on more than 40,000 adults showed that 2% of people who received the mFLUSIVA vaccine (called mRNA-1010 before FDA approval) developed a laboratory-confirmed case of flu, verified through testing and symptoms reports¹. By comparison, 2.8% of those who received a standard dose of a comparator non-mRNA vaccine developed symptoms.

The tangled history of mRNA vaccines

“The key questions regarding immunogenicity, efficacy and safety have been addressed, which enabled the licensure of mFLUSIVA,” said Raffael Nachbagauer, vice-president of infectious-disease research at Moderna in Cambridge, Massachusetts, who is involved in mFLUSIVA trials.

But scientists still have questions about how this vaccine will perform when it’s rolled out to millions of people. Moderna has agreed with the FDA to conduct a confirmatory phase IV trial to research the efficacy relative to an enhanced vaccine in people aged 65 and older, says Nachbagauer.

Better flu immunity?

The mFLUSIVA vaccine works by delivering mRNA molecules encoding the flu virus’s hemagglutinin surface protein, packaged in a lipid nanoparticle that carries it into cells. Cells then translate the mRNA into hemagglutinin protein, which the immune system recognizes and subsequently builds antibodies against.

Clinical studies evaluating the efficacy of mFLUSIVA found that it had a 26.6% relative reduction in confirmed flu cases compared with a standard influenza vaccine. The investigation tested antigens from the three 2024–25 strains that were recommended by the World Health Organization in time for the corresponding Northern Hemisphere influenza season.

The study also found that mFLUSIVA was well tolerated by most participants. Adverse side effects were predominantly mild to moderate, with injection-site pain, fatigue and headache the most frequently reported. Side effects were more common in people who received the mRNA vaccine versus a standard dose vaccine — for example, injection-site pain was reported more than twice as often with mFLUSIVA as with the standard-dose comparator.

The ghost of influenza past and the hunt for a universal vaccine

A separate study² in people over the age of 65 comparing mFLUSIVA with licensed comparators contributed to mFLUSIVA’s accelerated approval in the 65-and-older age group. It measured participants’ antibody responses to flu rather than flu-like symptoms, and found that a single dose of the mRNA flu vaccine produced a stronger antibody response than did existing standard-dose and high-dose flu shots.

“A relative improvement over a standard-dose influenza vaccine is already clinically meaningful,” says Federico Martinón-Torres, head of paediatrics at the University Clinical Hospital of Santiago de Compostela, Spain.