Flu Shot Efficacy Varies, mRNA Technology Shows Promise

The effectiveness of flu shots can fluctuate significantly from year to year, sometimes offering only a 20% to 30% reduction in the risk of illness.

Messenger RNA technology, or mRNA, has emerged as a potentially superior method for improving flu vaccine effectiveness, in part because it can be quickly updated to represent the flu strains currently circulating.

Recent findings shared by the New England Journal of Medicine revealed that Moderna’s mRNA flu vaccine provided better protection against illness compared to the standard flu shot during a Phase 3 clinical trial.

The data indicated the mRNA vaccine outperformed the traditional shot by approximately 27%. This is a hopeful sign for the vaccine’s approval, especially after the FDA rejected Moderna’s initial submission earlier this year.

To date, no mRNA-based flu vaccine has received approval globally. Notably, Moderna’s flu and COVID-19 vaccines utilize the same mRNA technology.

“These impressive results would likely challenge the FDA to refuse approval without substantial justification,” commented Dorit Reiss, a vaccine policy expert at the University of California, San Francisco.

The trial, sponsored by Moderna, involved over 40,000 adults aged 50 and older who were randomly assigned to receive either the mRNA vaccine or one of four standard flu shots during the 2024–2025 flu season. Generally, older adults face higher risks for severe complications from the flu than younger populations. The study was conducted across 301 sites in 11 countries, including the U.S.

Results showed that the incidence of illness was lower among those receiving the mRNA flu vaccine—around 2%, in contrast to 2.8% for the standard shot.

While side effects like fatigue, headaches, and arm discomfort were more common in the mRNA group, they were typically mild and short-lived, resembling reactions often seen with traditional flu shots.

An mRNA flu vaccine could make a substantial difference in preventing the flu. Traditional flu shots require months to produce, leading health officials to select strains up to a year in advance of peak flu season. Such a delay can result in mismatched strains. For instance, a new H3N2 variant emerged last summer, which raised concerns about the effectiveness of flu shots that targeted other strains.

Unlike traditional methods, mRNA vaccines can be developed more rapidly, providing health officials with the ability to make timely decisions regarding circulating strains.

“Faster vaccine development could help better align new vaccines with emerging influenza viruses,” stated Dr. Jesse Goodman, an infectious disease specialist at Georgetown University Medical Center and former FDA chief scientist.

Earlier this year, the FDA rejected Moderna’s application, citing that the company did not test its vaccine against the most effective treatment for adults aged 65 and older. Instead of comparing it to a higher-dose flu shot usually recommended for that demographic, Moderna chose a standard flu shot for comparison—a decision criticized by an FDA official for potentially exaggerating efficacy. Moderna responded by asserting that they followed the regulatory guidance as discussed.

According to the trial data, the mRNA vaccine was similarly effective for those 65 and older, where around 1.9% contracted the illness versus 2.6% for the standard version.

Following public scrutiny, the FDA allowed Moderna to revise its application, proposing separate submissions for adults 50 to 64 and an expedited review for those aged 65 and above, with the promise of a follow-up trial.

Goodman added that, despite the absence of a high-dose flu shot comparison for older adults, the superior performance of the mRNA vaccine against standard flu shots suggests it holds at least comparable benefits.

“The evidence should strongly support FDA approval of the vaccine,” he asserted.

The FDA is anticipated to render a decision regarding the mRNA flu shot by August 5, as indicated by Moderna. The company declined to comment on the Phase 3 trial results.

Under Robert F. Kennedy’s leadership, the Department of Health and Human Services has adopted a more stringent stance on vaccines, particularly those utilizing mRNA technology. Health Secretary Kennedy has labeled mRNA vaccines as especially risky, referring to the mRNA COVID-19 vaccine as “the deadliest vaccine ever made.”

In August, HHS canceled nearly $500 million in funding aimed at mRNA vaccine research, underlining concerns regarding this technology.

In May, Moderna retracted its request for approval of a combined flu and COVID-19 mRNA vaccine after the FDA sought additional data.

Health experts hope that the administration will review Moderna’s mRNA flu vaccine impartially. Dr. Peter Hotez, dean of the National School of Tropical Medicine at Baylor College of Medicine, emphasized that the unpredictability of emerging pathogens makes it essential to keep multiple vaccination technologies available.

“For Ebola in 2019, it was the VSV technology, and for COVID-19 in 2020, it was mRNA,” Hotez noted. “Limiting our arsenal of vaccine technologies for ideological reasons reduces our capability to safeguard public health.”