Pfizer’s mRNA flu shot outperforms standard flu vaccine in late-stage trial

Pfizer’s mRNA flu vaccine outperformed the standard flu shot in a Phase 3 clinical trial, according to results published Wednesday in the New England Journal of Medicine.

The vaccine uses the same messenger RNA technology as Pfizer’s Covid shot. Ever since the mRNA Covid vaccines were approved in 2020, experts have looked at flu as one of the next logical applications for the technology. No country has approved an mRNA flu vaccine.

Dr. Buddy Creech, a pediatric infectious disease physician at Vanderbilt University Medical Center in Nashville, Tennessee, said Pfizer’s mRNA flu vaccine could be “a game-changer,” potentially providing a closer match to the strains in any given flu season. One big reason flu shots aren’t as effective as they can be is because they aren’t a good match for the circulating virus.

Because it takes months to manufacture a traditional flu shot, Creech said, scientists must choose the strains to include in the vaccine about six to eight months before flu season begins. Developing an mRNA shot is typically faster, which could allow those decisions to be made later in the year — and give scientists more flexibility to pivot if the circulating strain changes.

“There remains a significant need for improved approaches to prevent influenza,” Creech said. The trial results, he said, provide “proof” that the mRNA shot has an advantage over traditional flu vaccines.

Pfizer, however, may face an uphill battle to get the new vaccine approved, said Dr. Peter Hotez, dean of the National School of Tropical Medicine at Baylor College of Medicine in Texas and co-director of the Texas Children’s Hospital Center for Vaccine Development.

Health Secretary Robert F. Kennedy Jr., an anti-vaccine activist, has downplayed the benefits of vaccines and has singled out vaccines made with mRNA as particularly dangerous, calling the mRNA Covid vaccine “the deadliest vaccine ever made.” Several states have introduced legislation to ban mRNA vaccines.

In August, the Department of Health and Human Services canceled nearly $500 million in funding into mRNA vaccine research.

In May, Moderna, which also makes an mRNA Covid vaccine, withdrew its application seeking approval for its combination flu and Covid mRNA shot after the Food and Drug Administration asked for more data.

“Despite all the advantages of mRNA, I’m concerned that our current DHHS has no or little interest in the science,” Hotez said.

HHS did not immediately respond to a request for comment.

Dr. Kelly Lindert, Pfizer’s vice president of clinical research and development, said in an email that the company is “in discussion with health authorities on the path to licensure of mRNA influenza vaccines.” She declined to comment on the timeline for submission or approval.

The new trial, funded by Pfizer, compared the company’s mRNA shot to Fluzone, one of the most widely used seasonal flu vaccines in the U.S. More than 18,000 adults, most of them in the U.S., were randomly assigned to get either shot during the 2022-2023 flu season. Other trial sites included South Africa and the Philippines.

The trial found Pfizer’s shot cut flu-like illnesses by 34.5% compared to Fluzone — 57 cases in the mRNA group versus 87 cases in the Fluzone group. Nearly all infections were caused by two common influenza A strains: H3N2 and H1N1. The Pfizer vaccine also protected against two influenza B strains, the Victoria strain and the Yamagata strain. The Yamagata strain fell out of circulation during the Covid pandemic.

Both flu shots caused side effects, including arm pain and fatigue, though they were more common in people who got the mRNA flu shot compared to the traditional vaccine. A small percentage — 5.6% — of people who got the mRNA vaccine reported fevers, compared to 1.7% in the traditional flu shot group. Most side effects were mild to moderate and went away within 1 to 2 days.

Creech said it’s not surprising that the mRNA vaccine caused more side effects, given that it generated a stronger immune response.

“In some ways, this is like training for a race,” Creech said. “We may have a little bit of muscle soreness or fatigue after a training run, but by having a little bit of discomfort then, we can avoid overwhelming fatigue or soreness during the race.”

Lindert said it’s plausible people are reporting more side effects due to “the cascade of events from the activation of the immune response.”

“The relationship between side effects and immune responses is the source of ongoing discussion in the scientific community,” Lindert said.

Moderna is also still working on a stand-alone mRNA flu vaccine.

In June, the company reported results from a late-stage trial in older adults, finding its mRNA flu shot was about 27% more effective than an approved flu shot made by GSK. The company said people who got its shot had side effects that were similar to those seen with other flu vaccines.

Creech said “not all mRNA vaccines are created the same,” adding that it’s not surprising Pfizer’s and Moderna’s shots could have different efficacy levels and side effect profiles.

In an emailed statement, a spokesperson for Moderna said the company plans to file for approval for its stand-alone flu vaccine by January 2026.