Trivalent mRNA Flu Shot Shows Stronger Protection Than Traditional Vaccines in New Study

A new type of flu vaccine built with messenger RNA (mRNA) technology — the same platform used in many COVID-19 shots — has outperformed standard flu vaccines in a large clinical trial involving adults aged 50 and older. The findings suggest that mRNA flu vaccines could offer better protection during flu season, though they also come with a higher chance of temporary side effects like sore arms and fatigue.

The study, called the Fluent trial, tested an experimental vaccine known as mRNA-1010. It was designed to protect against three strains of influenza: two A strains (H1N1 and H3N2) and one B strain (Victoria). Researchers compared this new shot against standard-dose flu vaccines that are already approved and widely used.

For anyone who has ever wondered whether the annual flu shot is worth the hassle — or if a newer option might work better — this research offers important clues. Here is what the study found, what it means for your health, and what experts say about the future of flu prevention.

What the Study Found: Numbers That Matter

The results, published in the New England Journal of Medicine, show a clear advantage for the mRNA vaccine. Among more than 40,000 participants aged 50 and older, lab-confirmed influenza A or B cases occurred in only 2% of those who received mRNA-1010. In the group that got standard flu shots, the rate was 2.8%.

That difference translates to a relative vaccine efficacy of 26.6%. In plain language, people who got the mRNA shot were about 27% less likely to get the flu compared with those who received a traditional vaccine. The results were statistically significant, meaning they were unlikely to be due to chance.

The protection was even more noticeable when researchers looked at cases that required medical attention. People who got mRNA-1010 had a 33.7% lower risk of needing to see a doctor, visit an urgent care center, or go to the emergency room for flu-related illness. For serious cases that led to hospitalization or emergency care, the mRNA vaccine reduced risk by 47.9%.

How This Affects Older Adults

Older adults are especially vulnerable to severe flu complications. Every year, thousands of people aged 65 and older are hospitalized or die from influenza. The study included more than 19,000 participants in this age group. Among them, the mRNA vaccine showed a relative efficacy of 27.4% compared with standard shots.

The researchers noted that this level of protection is similar to what is seen with “enhanced” flu vaccines — such as high-dose, adjuvanted, or recombinant shots — that are already recommended for older adults. That is an encouraging sign because those enhanced vaccines are often more expensive and harder to produce than standard shots.

Side Effects: What to Expect

Here is the trade-off: the mRNA vaccine caused more short-term side effects than standard flu shots. These are called “reactogenicity events,” and they are a sign that your immune system is responding to the vaccine.

Common side effects with mRNA-1010 included:

• Injection-site pain: 65.8% (compared with 29.8% for standard vaccines)
• Fatigue: 45.1% (vs. 20.3%)
• Headache: 37.8% (vs. 18.0%)
• Muscle aches: 35.4% (vs. 11.6%)

The good news is that most of these reactions were mild to moderate and went away on their own within a few days. Serious adverse events were rare and occurred at similar rates in both groups — 2.2% in the mRNA group and 1.9% in the standard vaccine group. Only a handful of these were considered related to the vaccine.

No cases of acute myocarditis, myopericarditis, or pericarditis were reported in the mRNA group within 42 days of vaccination. These heart-related conditions were a concern with some mRNA COVID-19 vaccines, especially in younger men. The researchers specifically looked for them and found no signal in this flu vaccine trial.

Why mRNA Technology Matters for Flu Shots

The mRNA platform offers several advantages over traditional flu vaccine production. Most current flu vaccines are grown in chicken eggs, a process that takes months. If the circulating flu strains change during that time — which they often do — the vaccine may not match well.

mRNA vaccines can be updated much faster. Instead of growing viruses in eggs, manufacturers simply change the genetic code in the vaccine. This speed was proven during the COVID-19 pandemic, when mRNA vaccines were developed and tested in record time.

“This approach could allow for better strain matching and more effective protection each season,” the researchers wrote in their summary.

The Road to FDA Approval

The path to market has not been completely smooth. Moderna, the company developing mRNA-1010, publicly disagreed with the U.S. Food and Drug Administration (FDA) earlier this year about the trial design. The FDA initially refused to review Moderna’s application because the study did not include a specific high-dose vaccine recommended for people 65 and older as a comparison.

After Moderna provided additional data from a separate trial that used a high-dose shot for older adults, the two sides reached a compromise. Moderna agreed to seek full approval for adults aged 50 to 64 and accelerated approval for those 65 and older. The company will need to conduct an additional study once the vaccine is on the market.

A decision from the FDA is expected by August 5. Moderna says it hopes to make the vaccine available later this year.

What About Other mRNA Flu Vaccines?

Moderna is not the only company working on mRNA flu shots. Pfizer has also developed a quadrivalent mRNA flu vaccine — one that targets four strains instead of three. In a randomized trial published last year, that vaccine showed a 34.5% greater relative efficacy compared with a standard inactivated quadrivalent flu vaccine in people aged 18 to 64. It also met criteria for noninferiority and superiority.

Having multiple mRNA flu vaccines in development could mean more options for consumers and more competition to keep prices reasonable.

Practical Takeaways for Readers

What this means for your next flu shot:

• If approved, mRNA flu vaccines could offer better protection than standard shots, especially for older adults.
• You may experience more short-term side effects like soreness, fatigue, or headache, but these are usually mild and brief.
• The vaccine appears safe, with no increased risk of serious heart problems in the trial.

What experts generally recommend:

• The best flu vaccine is the one you actually get. Even standard shots reduce your risk of illness, hospitalization, and death.
• If you are 65 or older, talk to your doctor about whether an enhanced vaccine — high-dose, adjuvanted, or recombinant — is right for you. mRNA vaccines may eventually join that list.
• Getting vaccinated every year is still the most effective way to protect yourself and your community from seasonal flu.

Looking Ahead

The Fluent trial results are promising, but they do not mean the end of traditional flu vaccines overnight. Regulatory decisions, manufacturing scale-up, and public acceptance will all play a role in how quickly mRNA flu shots become available.

Still, the consistency of protection across different age groups, flu strains, and levels of illness severity suggests that mRNA technology could change how we fight influenza. As one of the researchers put it, “The findings support the role of mRNA-1010 in improving influenza prevention.”

For now, the message is clear: science is moving fast, and the annual flu shot — already a lifesaving tool — may soon get even better.

Source: MedPage Today