New Delhi: The US Food and Drug Administration (FDA) last week approved the world’s first flu vaccine developed using messenger RNA (mRNA) technology by American pharmaceutical company Moderna, months after the regulator refused to review the company’s application.
Called mFLUSIVA, the vaccine was cleared 5 August. The approval so far covers adults aged 50 to 64, while those aged 65 and older have received accelerated approval, which allows the vaccine to be used now while Moderna conducts further studies that could lead to full approval, The Washington Post reported.
Moderna expects doses of the vaccine to be available for the 2026-27 respiratory virus season.
The approval brings mRNA technology, used in Covid-19 vaccines made by Moderna and Pfizer-BioNTech, into seasonal influenza vaccination for the first time. Most existing flu vaccines give the body a protein from the virus, so the immune system can learn to recognise it. An mRNA vaccine instead gives instructions to the body’s cells to make that protein, allowing the immune system to prepare a response.
In Moderna’s clinical trial, mFLUSIVA was nearly 27 percent more effective than a standard-dose flu vaccine.
“Flu remains a significant public health challenge, and mFLUSIVA provides an important new option for America’s seniors,” Moderna CEO Stéphane Bancel said in a press statement.
“This approval also reflects the ongoing potential of our mRNA platform to help address important public health challenges through continued scientific innovation,” he added.
The route to approval, however, was unusual. Earlier this year, the FDA declined to review Moderna’s application—a rare move against a large drugmaker which had conducted a large, largely favourable trial, according to The Washington Post.
The agency questioned whether the study was adequate and well controlled, particularly because Moderna had compared its vaccine with a GSK flu vaccine that was not considered the best available option.
The refusal came from Dr Vinay Prasad, then head of the FDA’s vaccine division. Public criticism followed, and FDA Commissioner Dr Marty Makary later described the decision as part of the regulator’s “ongoing dialogue” with manufacturers. The FDA subsequently agreed to review the application, The Washington Post reported.
The episode has also unfolded against a wider political debate over mRNA vaccines in the US, with Health Secretary Robert F. Kennedy Jr. having repeatedly questioned the technology used in Covid-19 vaccines.
How is mRNA flu vaccine different?
According to Dr Gagandeep Kang, noted microbiologist and virologist and Director of Enteric & Diarrheal Diseases, Diagnostics, Genomics, Epidemiology, and Modeling in Global Health at the Bill & Melinda Gates Foundation, the approval introduces mRNA as a new platform for flu vaccination.
“This is the first flu vaccine approved on the mRNA platform,” Dr Kang, who was also formerly a professor of microbiology at the Christian Medical College (CMC) in Vellore, said.
“The previous flu vaccines have been of basically three types,” she added. “In one, the flu virus is grown in fertilised chicken eggs to make the vaccine, while the other is made by growing the virus in laboratory-grown cells. Both the vaccines are injected while the third is a nasal vaccine, which is administered as a spray in the nose rather than through an injection. mFLUSIVA is the fourth type,” she said.
Most conventional flu vaccines give the body a protein from the flu virus. The immune system recognises this protein and learns to fight the virus.
The mRNA vaccines take a different approach. The messenger RNA carries instructions that cells use to make proteins. In a mRNA vaccine, scientists package these instructions inside tiny fat particles called lipid nanoparticles, which help deliver them into cells.
Once inside a cell, the mRNA reaches the ribosome, the part of the cell that makes proteins. The ribosome reads the instructions and makes the flu protein. The immune system then recognises this protein and prepares to fight the virus.
“What is different about mRNA vaccines is you don’t give the protein, you give the genetic sequence for making the protein,” Dr Kang told ThePrint.
The mRNA provides temporary instructions and is then broken down. It does not become part of a person’s DNA.
Moderna reported that mFLUSIVA was nearly 27 percent more effective than a standard-dose flu vaccine in its large clinical trial. Dr Kang described it as “a very good result”, noting that flu vaccine effectiveness can be around 40 to 50 percent in a season, depending partly on how closely the vaccine matches circulating strains.
In the trials, Moderna compared mFLUSIVA with existing flu vaccines. More than 40,000 participants in one trial received either the mRNA vaccine or a standard-dose flu vaccine. A second trial compared it with a high-dose flu vaccine used for older adults.
Dr George M. Varghese, Professor and Head of the Department of Infectious Diseases at Christian Medical College (CMC), Vellore, said using an existing flu vaccine as a comparison was scientifically reasonable.
Explaining why the vaccine has been approved for older adults, Dr Kang said people in this age group are more likely to develop severe influenza, but vaccines can also be less effective as people get older. This makes it important to assess how well mFLUSIVA protects people aged 65 and above.
The FDA has, therefore, given mFLUSIVA accelerated approval for this age group and asked Moderna to conduct further studies for those over 65.
How mRNA vaccines became known
Although mRNA vaccines became widely known during Covid-19, the science behind them dates back decades. Dr George M. Varghese said mRNA was discovered in 1961, and research into using it as a vaccine platform continued for decades after. He described mRNA as a “second generation” approach to vaccine development.
The Covid-19 pandemic was the major turning point, showing that the platform could be developed, manufactured and deployed on a large scale. Moderna and Pfizer-BioNTech used it to develop Covid-19 vaccines in record time.
That speed could be particularly useful for influenza, Dr Varghese said, adding that an mRNA vaccine could potentially be developed and manufactured in about six weeks, compared with about six months for a conventional flu vaccine.
But faster production does not remove the challenge of predicting which flu strains will circulate. Epidemiologist and public health researcher Dr Chandrakant Lahariya said the World Health Organisation tracks circulating strains and recommends the composition of seasonal vaccines, but the strains that eventually dominate can vary by region and season.
The shorter manufacturing time could nevertheless allow manufacturers to adjust vaccines closer to the time they are needed. Lahariya said it could also make it possible to develop separate vaccines for Northern and Southern Hemisphere seasons.
But the technology has limitations.
“mRNA vaccines are still relatively new compared with conventional vaccine platforms, which have been used for decades. The limited scientific data available so far means researchers are still learning about the technology, including its advantages and disadvantages,” Dr Verghese told ThePrint.
He added that more clinical trials and real-world data will be needed to establish how much better mRNA vaccines are than existing vaccines.
Why did the FDA initially refuse to review it
The FDA’s initial objection centred on Moderna’s clinical trial and the vaccine used as its comparison. In February, Dr Vinay Prasad, then head of the FDA’s vaccine division, said the company had not provided an “adequate and well-controlled” study. The agency questioned why Moderna had compared mFLUSIVA with a standard-dose GSK flu vaccine rather than a high-dose vaccine used for older adults.
According to The Washington Post, the FDA had previously recommended a high-dose comparison for people aged 65 and above. Moderna proceeded with a standard-dose comparison, prompting the agency to initially decline to review the application.
Dr Varghese said he did not see a fundamental problem with the comparison. “That approach, published in May this year, there is no issue with that. That’s a very fair comparison,” he said.
The FDA later agreed to review the application and ultimately approved the vaccine.
“The biggest misconception is that vaccines do not protect. The argument that the risks outweigh the benefits is not supported by what we know about vaccines used in immunisation programmes. The benefits outweigh the risks. No regulator is going to approve a vaccine for healthy people if the potential harm is greater than the benefit,” Dr Kang said.
In June, FDA vaccine advisers unanimously concluded that the benefits of Moderna’s flu vaccine outweighed its risks for adults aged 50 to 64 and those aged 65 and above, according to The Washington Post.
The FDA has reported higher rates of temporary injection-site reactions and fatigue with the mRNA vaccine than with traditional flu vaccines. Experts told ThePrint that these reactions were generally mild and short-lived.
Dr Kang said no major safety concern specific to the mRNA platform has emerged so far, but added that rare side effects can become apparent only after a vaccine is used on millions of people, making continued post-marketing monitoring important.
(Edited by Viny Mishra)
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