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Expert Reaction
These comments have been collated by the Science Media Centre to provide a variety of expert perspectives on this issue. Feel free to use these quotes in your stories. Views expressed are the personal opinions of the experts named. They do not represent the views of the SMC or any other organisation unless specifically stated.
Associate Professor Sanjaya Senanayake is a specialist in Infectious Diseases and Associate Professor of Medicine at The Australian National University
"mRNA vaccines became prominent during the COVID-19 pandemic, but they had been researched for some time before then with different infections. This current randomized controlled trial looked at just under 20,000 participants aged between18 and 64 who were given either a mRNA flu vaccine or the standard flu vaccine. Both vaccines contained two strains of influenza A and two strains of influenza B. They compared the vaccines in three ways: their ability to prevent people getting sick with flu, the amount of antibodies generated by each vaccine, and the side effect profile. The outcomes were that the mRNA vaccine was better than the standard vaccine at preventing a flu illness, and at least as good in terms of antibody responses. However, the mRNA vaccine was more likely to cause systemic side effects like fevers. The mRNA vaccine may not have been quite as good against the B strain of flu, but the numbers were too small to make a meaningful conclusion. Overall, this was a good study because it was randomised. It covered three countries, which meant that vaccine responses could be assessed in different population groups. However, it would have been nice to see people 65 or over included in the study as they represent a group prone to complicated influenza. Also, the mRNA caused more side effects than the standard flu vaccine. While these tended to not be serious, in the current climate where vaccine suspicion is relatively high, the result may make it just that bit harder to get the mRNA vaccine accepted. Also, the issue of cost wasn't mentioned. This would be important to determine if the reduction in cases of influenza would be cost effective with the new mRNA vaccine versus the current flu vaccines. After all, a government will have to fund the program."
Last updated: 19 Nov 2025 11:09am
Professor Paul Griffin is the Director of Infectious Diseases at Mater Health Services and the Head of the Mater Clinical Unit for the University of Queensland School of Medicine
"The impact of influenza remains very significant and is often understated. So far this year, there have been over 440,000 notifications of laboratory-confirmed influenza and approximately 1000 deaths due to influenza recorded in Australia. Vaccination rates remain low, and this will undoubtedly have had an impact on the burden of disease we have seen this year.
Using mRNA as a vaccine platform is not a new concept. While it became prominent as a result of being the most commonly used platform for COVID-19 vaccines (of which now more than 10 billion doses have been administered), it was first used in clinical trials in humans more than 10 years ago. mRNA vaccines for COVID-19 in large clinical trials and extensive real-world evidence have been shown to be highly effective.
Given the burden of disease and challenges and limitations with existing influenza vaccines, as well as the added potential of the mRNA platform, applying this to influenza is a logical progression with many potential benefits.
In this study, a modRNA vaccine is used in which components of the mRNA (nucleosides) are replaced by naturally occurring modified nucleosides (including pseudouridine for example). This improves performance, including being translated more efficiently. The use of modRNA as a platform for influenza has many potential advantages over traditional egg-based influenza vaccines, including being quicker and easier to make and likely to make it quicker and easier to match circulating strains.
This publication reports on a large clinical trial in which 18746 participants aged 18 to 64 were randomised in a blinded fashion to receive either the modRNA vaccine (9225) or a control vaccine, Fluzone (9251). The modRNA vaccine had statistically superior efficacy over the control vaccine with greater immune responses and 30 fewer cases with a relative efficacy of 34.5%. It was also associated with more reactogenicity events; however, these were mostly expected local or systemic reactions graded as mild to moderate in severity. More severe events were low and similar in the two trial groups.
Given the impact of influenza and the limitations of existing influenza vaccine strategies and the potential benefits of an mRNA influenza vaccine, demonstrating superior efficacy with an acceptable safety profile in a large phase 3 clinical trial of a modRNA influenza vaccine is another important step toward adding mRNA vaccines to the tools available to combat influenza."
Last updated: 19 Nov 2025 11:06am
Associate Professor Vinod Balasubramaniam is a Molecular Virologist and the Leader of the Infection and Immunity Research Strength from the Jeffrey Cheah School of Medicine & Health Sciences at Monash University in Malaysia
"A major new study published in the New England Journal of Medicine shows that Pfizer's mRNA flu vaccine offers better protection for adults under 65 than a current standard shot. This is a significant step in using the technology pioneered during the COVID-19 pandemic to tackle seasonal influenza. However, the research also reveals important limitations, including weaker protection against one type of flu and more frequent side effects.
What the Study Found?
- In a large, global Phase 3 trial involving over 18,000 healthy adults (aged 18-64), the mRNA vaccine demonstrated a 34.5% higher relative efficacy at preventing lab-confirmed flu compared to a licensed inactivated vaccine (Fluzone).
- This improved protection was almost entirely driven by strong results against influenza A viruses (H3N2 and H1N1), which are often responsible for more severe seasonal outbreaks.
- However, the vaccine induced a weaker antibody response against influenza B strains. While there was too little flu B circulating during the trial to measure real-world effectiveness, this is a noted weakness.
- The mRNA vaccine not only generated higher antibody levels against flu A but also triggered a much more robust "T-cell" response. This part of the immune system acts like specialised infantry and can lead to broader and longer-lasting protection.
- The trade-off for better protection was higher reactogenicity. Recipients of the mRNA vaccine reported more frequent side effects like fatigue, headache, muscle pain, and fever. These were mostly mild to moderate and short-lived (1-2 days), but were about three times more common for some symptoms.
What are the implications?
This trial successfully demonstrates that mRNA technology can create a more effective seasonal flu vaccine than a standard shot, offering key advantages like faster, more precise production and the potential for future combination vaccines. However, its limitations are notable: we only know it's better than an existing vaccine, not its exact standalone efficacy; the trial was limited to one season and excluded vulnerable groups like children and the immunocompromised; and most crucially, it showed no significant benefit for adults over 65, the group most at risk from severe flu, highlighting that this is a promising step forward but not a complete solution for all.
For Australia, which faces a significant flu burden each year (e.g., over 300,000 cases and more than 1000 deaths in 2024), this new vaccine represents a promising tool.
- If approved by the Therapeutic Goods Administration (TGA), healthy Australian adults could soon have access to a vaccine that provides superior protection against the often-dominant influenza A viruses. This could mean fewer illnesses, reduced workplace absenteeism, and lower pressure on hospitals during the flu season.
- The decision to get this vaccine will involve weighing a higher chance of a day or two of side effects against a better chance of avoiding the flu altogether. Public health messaging will need to be clear about this balance to maintain trust and uptake.
- The lack of proven benefit in the elderly means that for now, existing high-dose or adjuvanted flu vaccines remain the best option for older Australians. This new mRNA vaccine is likely to be a complementary tool, not a one-size-fits-all solution.
This trial demonstrates the mRNA platform's success in improving influenza protection. The vaccine elicits a superior dual immune response: robust neutralizing antibodies and polyfunctional CD4+ and CD8+ T-cells, providing enhanced defence against dominant influenza A strains. This immunologic advantage translates to a significant reduction in lab-confirmed flu cases. While reactogenicity is higher, the safety profile is acceptable. This represents a pivotal advance in vaccinology, offering a more effective, rapidly adaptable tool for seasonal flu control, with potential for future combination vaccines."
Last updated: 19 Nov 2025 11:05am
Dr Emma Grant is Group Leader at the Institute for Molecular Science (LIMS) at La Trobe University
"The new Pfizer ModRNA influenza vaccine has just completed a Phase III clinical trial and is showing some promising results. This new vaccine uses mRNA technology, similar to that of COVID-19 vaccines, and trial data published by Fitz-Patrick et al. indicate that it offers some increased protection against seasonal influenza strains.
However, introducing mRNA technology into influenza vaccination brings exciting potential beyond these initial findings. Manufacturing mRNA vaccines is significantly faster than traditional methods, which rely on growing the virus in eggs or cells, a process that can take six months or more. Faster production means vaccine strains can be selected closer to the flu season, reducing the risk of mismatch with circulating viruses.
Moreover, as demonstrated with COVID-19 vaccines, mRNA technology can activate multiple arms of the immune system, including long-lived killer T cells that recognise multiple different influenza strains. Indeed, results from this study indicate that the new vaccine demonstrated some increased cellular responses compared to the traditional influenza virus vaccine tested. This capability moves us closer to the long-sought goal of a 'universal' influenza vaccine, one that provides broader and longer-lasting protection."
Last updated: 19 Nov 2025 11:04am
Dr Rodney Pearce AM is Chair of the Immunization Coalition
"A new vaccine that is safe and effective to help us reassure patients and health care providers (HCP) of the benefits of vaccination is a dream come true.
Vaccine rates for seasonal flu are down, so this phase 3 result with Pfizer's new influenza vaccine could be a welcome addition. It has shown its benefit over a licensed inactivated influenza vaccine in 3 countries with noninferiority of antibody and less infection, but only to Influenza A. The benefit seems to come at a cost of more side effects (5.6% cf 1.7%).
Further development of the mRNA vaccines (this is a Nucleoside-modified messenger RNA influenza vaccine) is in line with vaccines moving away from the traditional egg-based influenza vaccines.
Each flu season is different, but without evidence of protection for the B strain (B/Victoria) this needs further investigation.
Myocarditis or pericarditis has been a concern with the early mRNA vaccines, but as there is no reported incidence, it may be more a side effect of COVID vaccines rather than mRNA vaccines."
Last updated: 19 Nov 2025 11:03am
Professor Archa Fox is a Professor in the School of Human Sciences and the School of Molecular Sciences at The University of Western Australia
"This paper reports Phase 3 clinical trial results from Pfizer comparing its mRNA flu vaccine to a conventional flu vaccine, given over the course of a winter flu season. They found the mRNA vaccine performed better than conventional flu vaccines. Only 0.63% of people injected with the mRNA flu vaccine came down with the flu, compared to 0.95% of people injected with conventional flu vaccine coming down with the flu. This should help make a case for rolling out mRNA flu vaccines. Currently, the only mRNA vaccines in Australia are for COVID-19.
Interestingly, there was a slightly higher chance of getting muscle pain, fatigue and redness at the site of injection with the mRNA vaccine, but no cases of myocarditis. It seems the mRNA vaccines trigger a strong immune response. This matches another study this year that showed giving an mRNA vaccine in the 30 days before certain types of cancer treatment helps cancer patients' immune system tackle their disease.
Despite the strong anti-mRNA vaccine sentiment seen in some parts of the world and some corners of the internet, this study shows the mRNA vaccines are safe and effective. Australia has invested heavily to build up sovereign mRNA manufacturing capability. We should be well placed for rapid mRNA vaccine manufacturing in future pandemics, as well as getting local supplies of vaccines for annual shots."
Last updated: 18 Nov 2025 4:46pm
Professor Ian Barr is the Deputy Director of the WHO Collaborating Centre for Reference and Research on influenza, Victorian Infectious Diseases Reference Laboratory at the Peter Doherty Institute for Infection and Immunity
"The study by Fitz-Patrick and colleagues in the NEJM is the first peer-reviewed study to report on the efficacy (protection) of an mRNA vaccine in healthy adults aged 18-64 years of age. This was a large Phase 3 study involving some 18,476 participants performed mainly in the USA. The key result was the relative vaccine efficacy or (rVE) of the mRNA vaccine compared to the standard inactivated vaccine (Sanofi; Fluzone). A positive rVE indicates improved protection with the mRNA over the comparator and a negative rVE indicates a lower level of protection.
The results showed a rVE of 34.5% for the mRNA vaccine, meaning that the mRNA was a little over one-third better at protecting people than the standard vaccine. Safety measures for the two vaccines were similarly low, although the mRNA vaccinated group did have higher local and systemic reactions, including higher rates of pain, fatigue and headache with fever (≤ 40°C) in 5.6% of mRNA recipients compared to 1.7% of those given the standard vaccine.
Unfortunately, a further component of this trial involving subjects 65 years and over (not reported in this publication), and the main beneficiary of current influenza vaccines, failed to show enhanced protection with the mRNA vaccine having a rVE of -5.8%.
The Pfizer data is similar to unpublished data from a Moderna mRNA influenza vaccine in adults ≥50 y that had a rVE of 26.6% compared to a standard inactivated influenza vaccine (https://feeds.issuerdirect.com/news-release.html?newsid=4899326521164266&symbol=MRNA
Clearly, there is more work to do to optimise mRNA vaccines for the elderly and to reduce the reactogenicity of these vaccines for younger adults before mRNA vaccines will be viable alternatives to existing influenza vaccines."
Last updated: 18 Nov 2025 4:45pm
Associate Professor Seth Cheetham is Deputy Director of the BASE mRNA Facility at The University of Queensland
Influenza vaccines are a vital public health tool that reduce the impact of the seasonal flu outbreaks that kill hundreds of thousands of people globally each year. However, current vaccines provide imperfect protection, with an effectiveness of 41-55% at preventing influenza-related hospitalisation in the 2024-2025 U.S flu season. More effective influenza vaccines are urgently needed. A new article in the prestigious New England Journal of Medicine describes a new vaccine based on the same mRNA technology behind many COVID-19 Vaccines. The mRNA vaccine was developed by Pfizer, one of the companies behind the COVID-19 vaccines and was evaluated in a large Phase III trial. People vaccinated with mRNA were 34.5% less likely to have lab-confirmed influenza than those given traditional vaccines. The mRNA vaccine offered superior protection to Influenza A (one of the two main types), but too few Influenza B cases were detected in the study to determine if the vaccine was effective against these strains. Lab tests suggested that the new vaccine may not be as effective against B strains. The mRNA vaccine was safe, but an elevated rate of side effects, such as injection site pain and headache, was detected compared to traditional vaccines. Overall, this study provides important large-scale evidence that mRNA vaccines could be a powerful tool to reduce the burden of Influenza outbreaks. However, the higher levels of mild side effects associated with the mRNA vaccine may make this option less attractive to some patients and physicians compared to existing vaccines. The further development of mRNA vaccines that could combine reduced side effects with enhanced protection against both Influenza A and B strains could reduce the global impact of this devastating infection.
Last updated: 18 Nov 2025 4:40pm
Journal/
conference:
New England Journal of Medicine
Organisation/s: East-West Medical Research Institute, USA, Pfizer, Baylor College of Medicine, USA
Funder: Supported by Pfizer.
