Are mRNA Influenza Vaccines More Effective Than Seasonal Flu Vaccines? What the Science Says

On 5 August, the U.S. Food and Drug Administration (FDA) approved Moderna’s mRNA-based influenza vaccine, mFLUSIVA, for adults aged 50 to 64. The regulator has also accelerated the approval process for adults aged 65 and older. Moderna says the vaccine could be available “within weeks” for the 2026–27 influenza season in the United States.

Researchers welcomed the FDA decision, highlighting the potential advantages of mRNA vaccine technology for seasonal influenza. Unlike conventional flu vaccines, mRNA vaccines can be reformulated quickly to target influenza strains that are circulating during a given flu season. Emanuele Montomoli, a hygiene and public-health researcher at the University of Siena in Italy, described the approval as “very important” and said the technology could help address the long manufacturing timelines associated with traditional flu vaccines.

Regulators in the European Union, Canada and Australia are also reviewing the vaccine. Related mRNA influenza products have already been authorized in Europe. In April, the European Commission approved Moderna’s combined seasonal influenza and COVID-19 mRNA vaccine, mCombriax.

A clinical trial involving more than 40,000 adults found that 2% of participants who received mFLUSIVA, known as mRNA-1010 before FDA approval, developed laboratory-confirmed influenza based on testing and symptom reports.¹ By comparison, 2.8% of participants who received a standard-dose, non-mRNA influenza vaccine developed confirmed flu.

The complicated history of mRNA vaccines

“Important questions about immunogenicity, efficacy and safety have been addressed, making the approval of mFLUSIVA possible,” said Rafael Nachbagauer, vice president of infectious-disease research at Moderna in Cambridge, Massachusetts, which conducted the vaccine trial.

However, scientists say more evidence is needed to determine how well the mRNA flu vaccine will perform when administered to millions of people. Moderna has agreed with the FDA to conduct a confirmatory Phase IV study comparing mFLUSIVA with an enhanced influenza vaccine in adults aged 65 and older.

Could mRNA vaccines improve protection against seasonal flu?

mFLUSIVA delivers messenger RNA molecules that encode hemagglutinin, a surface protein found on influenza viruses. The mRNA is packaged inside lipid nanoparticles and delivered into human cells. Once inside, the cells use the genetic instructions to produce hemagglutinin. The immune system recognizes this viral protein and generates antibodies designed to help protect against future infection.

In a clinical study assessing the effectiveness of mFLUSIVA, the vaccine reduced confirmed influenza cases by 26.6% relative to standard influenza vaccines. The trial evaluated antigens from three influenza strains recommended by the World Health Organization for the 2024–25 Northern Hemisphere flu season.

Most participants tolerated mFLUSIVA well. Reported side effects were generally mild to moderate, with injection-site pain, fatigue and headache among the most common reactions. These effects occurred more frequently among people who received the mRNA vaccine than among those given the standard-dose comparator. Injection-site pain, for example, was reported more than twice as often after mFLUSIVA.

Ghosts of past influenza and the quest for a universal vaccine

Another study² compared mFLUSIVA with an approved influenza vaccine in adults aged 65 and older, supporting the vaccine’s accelerated approval for this age group. Researchers measured antibody responses to influenza rather than flu-like symptoms. They found that a single dose of the mRNA influenza vaccine produced stronger antibody responses than both standard-dose and high-dose seasonal flu vaccines.

“The relative improvement over standard-dose influenza vaccines is already clinically meaningful,” said Federico Martinon Torres, head of pediatrics at Santiago de Compostela University Hospital in Spain.