Could mRNA vaccines end brutal flu seasons?
A new mRNA flu vaccine was 34.5% more effective than a regular flu shot at preventing infection.
- 26 November 2025
- 3 min read
- by Priya Joi
A new mRNA vaccine against flu is showing substantially better protection than today’s standard shots in a pivotal clinical trial.
The Pfizer-developed ‘modRNA’ vaccine was 34.5% more effective than current vaccines at preventing illness caused by influenza A in a trial of over 18,000 people.
This reinforces hopes that the technology could transform seasonal influenza control and pandemic preparedness. The new vaccine had more mild side-effects than the regular flu shot, however serious side-effects were equally uncommon in either vaccine.
mRNA vaccine vs. traditional vaccines
Like the COVID-19 mRNA shots, the flu mRNA vaccines deliver genetic instructions that teach cells to make harmless pieces of the virus, training the immune system to recognise and fight infection without causing disease.
In modRNA vaccines, some of the building blocks in the mRNA are replaced with naturally occurring “modified” nucleosides, such as pseudouridine, which improves stability and allows cells to translate the message more efficiently, resulting in stronger immune responses from smaller doses.
Current seasonal flu vaccines are mainly inactivated trivalent or quadrivalent shots, grown in eggs and containing killed viruses from three or four circulating strains, a process that takes months and can lead to mismatches if the virus mutates.
By contrast, mRNA platforms can be updated and manufactured much more quickly, increasing the chances of matching the strains actually in circulation and offering a flexible tool in the face of sudden shifts or emerging influenza viruses with pandemic potential.
Stronger protection
In a large phase 3 trial published in the New England Journal of Medicine involving more than 18,000 adults aged 18 to 64, Pfizer’s modRNA flu vaccine showed 34.5% higher relative efficacy than a current flu vaccine (Fluzone) at preventing influenza A illness, with particularly strong responses to H1N1 and H3N2 viruses.
The researchers estimated that, compared with US-licensed vaccines used in the 2022–2023 season, overall effectiveness in adults under 65 could rise from about 44–54% to roughly 60–67% with the modRNA formulation.
The candidate did, however, generate weaker antibody responses to influenza B, and there was too little of this lineage circulating during the study to properly measure real-world protection against it.
Safety and trade-offs
People who had the mRNA vaccine were more likely to develop redness, swelling or pain at the injection site than those who received the traditional vaccine (70% vs. 43%). About two-thirds of the mRNA group developed a fever, headache, fatigue, chills, vomiting, diarrhoea, and muscle pain or joint pain, compared with about half of those given the traditional flu vaccine.
Serious side-effects remained low and of equal numbers in either group – and no-one developed myocarditis, an inflammation of the heart muscle.
Nevertheless, Bill Hanage, a professor of epidemiology at the Harvard T.H. Chan School of Public Health, told CIDRAP that “Researchers will need to reduce the number of side-effects to make mRNA shots palatable.”
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Replacing existing vaccines?
It’s not yet clear though, how modRNA flu vaccines would perform in populations at highest risk of severe outcomes, including older adults, people with underlying conditions and young children.
An accompanying editorial noted that, in recent US seasons, existing quadrivalent vaccines were 36–54% effective at preventing outpatient visits and 41–55% effective at preventing adult hospitalisations, arguing that even incremental improvements from next-generation platforms could represent a meaningful public health advance if benefits extend to vulnerable groups.
Because mRNA platforms are highly adaptable and can be scaled rapidly, they may also play a key role in future pandemic responses, allowing faster design and deployment of strain-matched vaccines when a novel influenza virus emerges.
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