Clinicians still struggle to protect patients from seasonal influenza each year, despite well-established vaccination programs. Although annual shots can significantly reduce severe complications and save thousands of lives, the medical community still faces biological, behavioral, and technical obstacles that limit the overall effectiveness of seasonal flu programs.
New vaccine technologies could help address some of these challenges, but important questions remain about their real-world implications.
Messenger RNA (mRNA) technology — a synthetic genetic code that instructs cells to build specific proteins that train the immune system — is being used to develop new seasonal flu vaccines.
The FDA recently approved mFLUSIVA, Moderna’s first mRNA-based seasonal influenza vaccine, for adults ages 50 and older. The decision marked an important milestone in influenza vaccine development and preventive medicine.
With this latest development, a question remains: Could mRNA technology help make influenza vaccine development more responsive to changing viruses?
Keep reading to learn more about the manufacturing process, strain selection, the research findings, and the clinical implications for providers and patients.
Influenza viruses undergo continual genetic changes, some of which alter the structure of viral surface proteins the immune system recognizes. These antigenic changes can affect how well vaccine-induced antibodies recognize circulating strains. Researchers monitor these changes and update seasonal flu vaccines each year to target the strains expected to circulate during the upcoming flu season.
The World Health Organization’s (WHO) Global Influenza Surveillance and Response System (GISRS) leads year-round surveillance of circulating influenza viruses to inform forecasting and modeling of strains that may arise during the upcoming flu season and what to target in vaccine development.
Vaccine development can occur through one of the following production technologies:
WHO sets a specific timeline for vaccine strain selection to give manufacturers enough time to develop, test, and distribute vaccines.
For the Northern Hemisphere, the seasonal influenza vaccine process typically follows a coordinated timeline, but the exact schedule can vary by region and manufacturer.
Because vaccine strain selection must be made months before the influenza season begins, manufacturers are working with predictions about which strains will circulate. If viruses evolve substantially after selection, the resulting vaccine may be less well matched to the strains that ultimately spread.
From February to October, influenza viruses can continue to mutate, which can pose the potential risk of vaccine “mismatch.” This occurs when a new mutation emerges and spreads after strain selection, meaning the updated vaccines won’t closely align with the dominant strain circulating that season. Most recently, vaccine mismatch occurred during the 2025-2026 flu season, with the virus, now known as subclade K, drifting from one of the recommended viruses after WHO’s strain selection.
These limitations have encouraged researchers and manufacturers to explore production platforms that may offer greater flexibility, such as mRNA technology. While no technology can eliminate the uncertainty of influenza evolution, using diverse manufacturing platforms may help strengthen vaccine preparedness and reduce reliance on a single production method.
mRNA is a temporary set of genetic instructions that cells can use to build a specific protein. In many mRNA vaccines, lipid nanoparticles package the instructions and help deliver them into cells. Once it’s done its job, enzymes degrade mRNA, and the cell modifies the newly synthesized protein as needed.
mRNA-1010 provides instructions for cells to produce the flu virus’s surface protein, hemagglutinin. The immune system recognizes the protein and develops an immune response against it.
Because mRNA doesn’t contain any live, weakened, or killed influenza virus, the platform may offer greater flexibility in how vaccine components are produced and updated. However, the speed of any vaccine update will depend on several factors, including strain selection, regulatory review, manufacturing capacity, quality control, and distribution.
The FDA’s approval of the mRNA vaccine could enable faster production of vaccine antigens without relying on growing influenza viruses in eggs. mRNA manufacturing could support rapid adjustments to vaccine composition because it relies on a cell-free, biochemical process rather than biological cell cultures.
One potential advantage of mRNA technology is that manufacturers can use a similar core production process while changing the DNA sequence that encodes the target antigen. This may reduce the need to redesign the entire manufacturing process when updating a vaccine. The process still involves steps such as in vitro transcription, purification, and lipid nanoparticle encapsulation.
If the platform allows vaccine composition to be updated much closer to the start of the influenza season, it could help reduce some sources of antigenic mismatch. Greater manufacturing flexibility could also offer operational benefits for public health systems and vaccine providers.
But while later strain selection is a potential platform advantage for influenza season, it doesn’t prove that every future vaccine will match circulating viruses better. Regulatory review, manufacturing capacity, quality control, and distribution timelines are still important.
In Phase 1 and 2 trials of the mRNA vaccine, researchers tested different dose levels to check the safety and immune response in healthy adults. Early data revealed that the vaccine successfully prompted the body to produce antibodies against targeted influenza strains. The platform’s cell-free production process has been proposed to reduce certain manufacturing steps and potentially shorten development timelines. However, the time to update, test, authorize, manufacture, and distribute a seasonal vaccine remains dependent on several operational and regulatory factors.
The Phase 3 clinical trial included 40,703 adults aged 50 and older during the 2024-2025 influenza season. Participants were randomly assigned to receive either mRNA-1010 or a licensed standard-dose influenza vaccine comparator.
Researchers reported a relative vaccine efficacy of 26.6 for mRNA-1010 compared with the standard-dose comparator. The result met the study’s prespecified superiority criteria.
Local and systemic reactions were more common with mRNA-1010 than with the comparator vaccine, although most were mild to moderate and temporary. The clinical trial didn’t identify a new safety signal during the study period.
New vaccine platforms don’t eliminate the need for strong vaccination recommendations and accessible preventive care. Clinicians should consider how vaccine availability, insurance coverage, transportation, scheduling, and communication affect uptake.
Future vaccine research also needs to include more diverse communities. Representation of Black participants has varied across clinical trials and disease areas. For that reason, examine clinical trial results for the populations represented in the study, how outcomes were measured, and whether the findings can be reasonably generalized to the patients they serve.
As influenza season approaches, patients may have questions about the new mRNA vaccine and whether it’s right for them. Clinicians should be prepared to explain what is known about its benefits, limitations, side effects, and eligibility while encouraging informed decision-making. Culturally responsive communication can help ensure that clinicians address patients’ questions and concerns without assuming one message will work for everyone.
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