On February 3, 2026, the US FDA issued a ‘refusal to file’ (RTF) letter to Moderna Inc. regarding their new mRNA vaccine developed against influenza. This decision generated considerable controversy worldwide, particularly given the current direction of vaccination policy in the United States towards a more conservative approach. However, that does not necessarily mean that the FDA’s refusal of a new mRNA influenza vaccine is connected to this policy shift.

Let us examine the facts.

How mRNA tech works

The new vaccine, named mRNA-1010, was developed by Moderna Inc., which also made an mRNA-based COVID-19 vaccine taken by millions of people worldwide during the pandemic (mRNA vaccines were not part of India’s mass vaccination programme). While most conventional viral vaccines insert actual pieces of a virus into the body, mRNA technology involves injecting “instructions” that signal our cells to produce a specific viral protein. The immune system then recognises this protein and mounts a response — without all the risks associated with an actual infection. As with other vaccines, this immune response may prevent or at least blunt a future infection. The advantage of mRNA technology, in the context of influenza, is that as viruses change their structure, vaccine design can be modified quickly to match the latest strains. In the event of an entirely new or novel virus emerging, the platform allows for relatively rapid development, offering a chance to limit the spread of future pandemics.

The success of mRNA vaccines during COVID-19 formed the basis of the, 2023 Nobel Prize in Physiology or Medicine recognising foundational work in mRNA technology that had been in development for decades. It was only expected that the same platform would be used to create new influenza vaccines. Influenza causes significant global illness and death each year, particularly among older individuals.

Vaccination reduces hospitalisation, death and even cardiovascular complications such as heart attacks and strokes. Annual vaccination is considered necessary because circulating viral strains continue to change, sometimes to such an extent that vaccines given in anticipation may not perfectly match strains that circulate later in the year. An mRNA-based influenza vaccine offers the theoretical advantage of faster strain updates.

Why was the refusal issued

Moderna is also developing a combined influenza and COVID-19 mRNA vaccine, and regulatory success of such a combination product in the U.S. may depend on approval of its standalone influenza component. The reasons for the decision are stated in the letter signed by Vinayak Prasad, Director of the FDA’s Center for Biologics Evaluation and Research. The agency issued a “refusal to file” because the application did not contain what it considers an “adequate and well-controlled” trial. Specifically, the control group used in the clinical study did not reflect what the FDA considers the “best available standard of care” in the United States for individuals aged 65 years and above.

The standard influenza vaccine contains 15 micrograms of antigen per strain. In contrast, older adults commonly receive high-dose influenza vaccines containing 60 micrograms per strain — four times the antigen amount. Alternatively, adjuvanted vaccines are used to enhance immune response in this age group. These enhanced vaccines are recommended because immune responses decline with age. The comparator used in the mRNA-1010 trial was a standard-dose (15 micrograms) quadrivalent influenza vaccine, commonly administered to younger adults.

Although also licensed for older individuals, it is not generally considered the preferred option in that age group when enhanced vaccines are already available. The FDA’s position was that if the new mRNA vaccine was intended for use in older adults, it should have been compared against a high-dose or adjuvanted vaccine that better reflects current clinical practice. By using a standard-dose comparator, the study may not have answered the relevant clinical question: how does the new vaccine perform against the strongest available alternatives? Controversy aside, it is important to understand what this decision does not represent: it is not a rejection of the mRNA platform. It is not a declaration that the vaccine is unsafe. It is not a statement that the mRNA influenza vaccine does not work.

Further options

Instead, the FDA stated that it “does not consider the application to contain a trial ‘adequate and well-controlled’ and is therefore, on its face, inadequate for review.” In regulatory language, this means the agency judged that the submitted study design itself failed to meet the evidentiary threshold required to proceed to full evaluation. The FDA letter outlines further procedural options available to the company, including a formal meeting to resolve the issue or the possibility of requesting that the application be reviewed despite the agency’s objections.

A third option is conducting a new study, but using a stronger comparator. However, performing a new head-to-head study against a higher-dose vaccine would involve additional cost and time, as well as the real possibility that the new vaccine may not demonstrate clinical superiority over existing alternatives.

The company had earlier published an immunogenicity study demonstrating a stronger antibody response for the mRNA-1010 vaccine, compared with both standard and high-dose influenza vaccines.

That study did not assess vaccine effectiveness in preventing disease. However, in the subsequent phase 3 study evaluating vaccine effectiveness in preventing influenza, the company chose to compare against the standard dose vaccine—and not the high dose vaccine. In that study, the rate of laboratory-confirmed influenza was about 26.6% lower in those who received the mRNA vaccine compared with those who received a standard-dose flu shot.

What next

This is encouraging — but it is unclear whether it would perform better than the stronger high-dose or adjuvanted vaccines commonly given to older adults. In that sense, the FDA’s position appears straightforward. When entering a mature vaccine space where improved options already exist for older adults, comparison against the strongest available alternative becomes important. This principle extends beyond vaccines to the evaluation of new treatments for conditions ranging from cancer and hypertension to stomach ulcers.

Thus, the controversy surrounding this decision may be loud, but the scientific reasoning outlined in the letter is clear and specific. In summary, the debate here is not about the legitimacy of mRNA vaccines. It is about whether the right comparator was chosen in a clinical trial — and whether that design is sufficient for regulatory review. Demanding tighter standards for clinical trials before regulatory approval strengthens public confidence and safety in the long run.

(Dr. Rajeev Jayadevan, is convener, research cell, Kerala State IMA and co-chairman, National IMA COVID Taskforce. rajeevjayadevan@gmail.com )

Published – February 13, 2026 06:07 pm IST

Russia has developed an mRNA vaccine against cancer, Russian news agency TASS has reported. The vaccine will be distributed to cancer patients for free, General Director of the Radiology Medical Research Center of the Russian Ministry of Health, Andrey Kaprin, told Radio Rossiya.

The vaccine has been developed in collaboration with several research centers and is expected to be released for public use by early 2025.

The vaccine’s pre-clinical trials had shown that it suppresses tumor development and potential metastases, Director of the Gamaleya National Research Center for Epidemiology and Microbiology Alexander Gintsburg told TASS.

What Is An mRNA Vaccine?

mRNA or messenger-RNA vaccines use specific parts of the infectious agent like its protein, sugar, or coating. mRNA vaccine gives a message to our cells to make a protein or even just a piece of a protein which are like those of the virus. The protein then triggers an immune response inside our bodies.

Can AI Help Generate Personalised Cancer Vaccines?

Earlier, in an interview with TASS, Mr Gintsburg had said that the use of artificial neural networks could bring down the duration of computing required to create a personalized cancer vaccine to less an hour.

“Now it takes quite long to build [personalized vaccines] because computing of how a vaccine, or customized mRNA, should look like uses matrix methods, in mathematical terms. We have involved the Ivannikov Institute which will rely on AI in doing this math, namely neural network computing where these procedures should take about half an hour to an hour,” Russia’s vaccine chief said.

Pharmacist Lena Springmann prepares a Covid-19 vaccination with Pfizer/Biontech vaccine at a vaccination center in Halle, Germany, Monday, Jan. 11, 2021. The Nobel Prize in Medicine has been awarded to two scientists whose work led to mRNA vaccines against COVID-19.
| Photo Credit: AP

The 2023 Nobel Prize in physiology or medicine will go to Katalin Karikó and Drew Weissman for their discovery that modifying mRNA – a form of genetic material your body uses to produce proteins – could reduce unwanted inflammatory responses and allow it to be delivered into cells. While the impact of their findings may not have been apparent at the time of their breakthrough over a decade ago, their work paved the way for the development of the Pfizer-BioNTech and Moderna COVID-19 vaccines, as well as many other therapeutic applications currently in development. The 2023 Nobel Prize in physics likewise will go to a team of scientists who used lasers to clarify the behaviour of electrons, and many prior Nobels have honored basic research.

We asked André O. Hudson, a biochemist and microbiologist at the Rochester Institute of Technology, to explain how basic research like that of this year’s Nobel Prize winners provides the foundations for science – even when its far-reaching effects won’t be felt until years later.

Hungarian biochemist Katalin Kariko poses for a photo in Budapest, Hungary, May 27, 2021. Two scientists have won the Nobel Prize in medicine on Monday, Oct. 2, 2023 for discoveries that enabled the development of mRNA vaccines against COVID-19. The award was given to Katalin Karikó and Drew Weissman. Karikó is a professor at Sagan’s University in Hungary and an adjunct professor at the University of Pennsylvania.
| Photo Credit: AP

Hungarian-born scientist Katalin Kariko’s obsession with researching a substance called mRNA to fight disease once cost her a faculty position at a prestigious US university, which dismissed the idea as a dead end.

Now, her pioneering work — which paved the way for the Pfizer/BioNTech and Moderna Covid-19 vaccines — has won her the Nobel Prize in Medicine.

Kariko, 68, spent much of the 1990s writing grant applications to fund her research into “messenger ribonucleic acid” — genetic molecules that tell cells what proteins to make, essential to keeping our bodies alive and healthy.

She believed mRNA held the key to treating diseases where having more of the right kind of protein can help — like repairing the brain after a stroke.

But the University of Pennsylvania, where Kariko was on track for a professorship, decided to pull the plug after the grant rejections piled up.

Also Read | India-made mRNA vaccine priced at ₹2,292, will be available as a booster dose

“I was up for promotion, and then they just demoted me and expected that I would walk out the door,” she told AFP in an interview from her home in Philadelphia in December 2020.

Kariko didn’t yet have a green card and needed a job to renew her visa. She also knew she wouldn’t be able to put her daughter through college without the hefty staff discount.

She decided to persist as a lower-rung researcher, scraping by on a meagre salary.

It was a low point in her life and career, but “I just thought…you know, the (lab) bench is here, I just have to do better experiments,” she said.

The determination runs in the family — her daughter Susan Francia did go to UPenn, where she earned a master’s degree, and won gold medals with the US Olympic rowing team in 2008 and 2012.

Twin breakthroughs

By the late 1980s, much of the scientific community was focused on using DNA to deliver gene therapy, but Kariko believed that mRNA was also promising since most diseases are not hereditary and don’t need solutions that permanently alter our genetics.

First though, she had to overcome a major problem: in animal experiments, synthetic mRNA was causing a massive inflammatory response as the immune system sensed an invader and rushed to fight it.

Explained | Who is manufacturing India’s mRNA vaccine?  

Kariko, together with her main collaborator and co-winner Drew Weissman, discovered that one of the four building blocks of the synthetic mRNA was at fault — and they could overcome the problem by swapping it out with a modified version.

They published a paper on the breakthrough in 2005. Then, in 2015, they found a new way to deliver mRNA into mice, using a fatty coating called “lipid nanoparticles” that prevent the mRNA from degrading, and help place it inside the right part of cells.

Both these innovations were key to the Covid-19 vaccines developed by Pfizer and its German partner BioNTech, where Kariko is now a senior vice president, as well as the shots produced by Moderna.

Both work by giving human cells the instructions to make a surface protein of the coronavirus, which simulates an infection and trains the immune system for when it encounters the real virus.

Explained | How can mRNA vaccines help fight cancer? 

New treatments

Though she does not want to make too much of it, as a foreign-born woman in a male-dominated field, Kariko occasionally felt underestimated — saying people would approach after lectures and ask “Who’s your supervisor?”

“They were always thinking, ‘That woman with the accent, there must be somebody behind her who is smarter or something,'” she said.

Yet the Nobel is just the latest accolade for Kariko, who has won the Breakthrough Prize, the L’Oreal-UNESCO prize for women in science awards, among many others.

It is a far cry from the time when her late mother would call every year after prize announcements to ask why she hadn’t been chosen.

“I never in my life get (federal) grants, I am nobody, not even faculty,” she would reply with a laugh.

To which her mother would reply: “But you work so hard!”