One Flu Shot for Life? Michigan Researchers Take a Major Step

LCCN Staff Report

ANN ARBOR, Mich. — Every year, health officials face essentially the same problem: predict which influenza strains will circulate months in advance, then manufacture vaccines designed to protect against them.

Researchers at the University of Michigan are working on a vaccine that could eventually make much of that annual guesswork unnecessary.

A new nanoparticle vaccine developed by University of Michigan Engineering researchers successfully protected mice against three different strains of influenza, according to research presented Aug. 24 at the American Chemical Society’s fall 2026 conference.

Rather than targeting the highly variable proteins emphasized by conventional flu vaccines, the experimental vaccine targets a protein called M2, which changes much more slowly as influenza viruses evolve.

That distinction could be important. Traditional flu vaccines primarily generate immune responses against hemagglutinin, a protein that makes up much of the influenza virus surface but frequently mutates. Because of those changes, health officials monitor circulating strains and manufacturers formulate new vaccines for each flu season.

The Michigan researchers instead focused on M2, which is similar across influenza A viruses, including seasonal, swine and bird flu strains.

Current seasonal flu vaccines typically contain three or four influenza variants selected in advance based on which viruses researchers believe are most likely to circulate during the upcoming season. According to the University of Michigan, their effectiveness can vary considerably from year to year, particularly when the strains that ultimately spread differ from those selected for the vaccine.

That is one reason scientists have long pursued a so-called universal influenza vaccine — one capable of providing protection across multiple strains and potentially remaining effective as the virus changes.

“Our goal is to develop a broadly protective and more effective flu vaccine, so you don’t have to get a flu shot every season,” Fei Wen, a University of Michigan professor of chemical engineering and corresponding author of the study, told Michigan News.

The researchers ultimately envision something considerably more ambitious.

“Eventually, with enough effort and research, we believe that you might need one shot to be protected for life,” Wen said.

That remains a goal rather than a demonstrated result. The vaccine has so far been tested in mice, and researchers still need to determine how long the protection lasts before moving toward its potential use in people.

The vaccine uses virus-like particles, or VLPs, which resemble a virus closely enough to attract the attention of the immune system but cannot cause influenza. By presenting the M2 protein to the immune system on the surface of these particles, researchers hope to teach the body to recognize a feature shared by a much broader range of influenza A viruses.

In the animal experiments, the vaccine was tested against three influenza strains. The ability to protect mice against multiple strains is what makes the results particularly promising, although successful results in laboratory animals do not guarantee that a vaccine will produce the same protection in humans.

The technology is also notable for how the vaccine is manufactured.

Researchers genetically engineered ordinary baker’s yeast to produce large quantities of the M2 protein. The yeast is then processed so that it produces noninfectious, virus-like particles roughly resembling influenza viruses but covered with M2 protein.

Using yeast could provide another major advantage: speed.

According to the University of Michigan, the process could produce large quantities of vaccine in approximately one month. Conventional influenza vaccines produced using chicken eggs can require about six months.

The shorter production period could give scientists more time to identify circulating strains before manufacturing begins. More importantly, it could become particularly valuable during a pandemic or following the unexpected emergence of a new influenza strain, when months spent producing a vaccine can have enormous consequences.

The platform is also designed so researchers can alter it if the M2 protein itself changes.

“If a new M2 strain does emerge out of nowhere, we’ll be able to quickly edit the vaccine,” said Trang Hoang, a University of Michigan doctoral student in chemical engineering and first author of the study. “Our method could improve pandemic response time.”

The potential reach of such a vaccine extends beyond the familiar seasonal flu. Influenza A viruses circulate in humans and animals, and strains associated with birds and pigs have periodically raised concerns because of their potential to cross species and cause outbreaks.

A vaccine capable of targeting a relatively stable component shared among those viruses could therefore have implications not only for annual flu seasons but also for preparing for future influenza pandemics.

The researchers have licensed the technology to Esperovax, which is working to develop an oral version of the vaccine.

For now, however, the work remains experimental. The researchers’ next step is determining how long vaccinated mice remain immune to influenza — an important question if the technology is ultimately going to fulfill its promise of eliminating the need for an annual flu shot.

Even if the approach ultimately proves successful, considerable testing would still be required before such a vaccine could become available to the public. Human clinical trials would need to establish safety, determine appropriate doses and demonstrate that the broad protection seen in mice can be reproduced in people.

The research was partially funded by a National Science Foundation CAREER Award.

The research was reported by Sheila Waterhouse of Michigan News and published by University of Michigan Engineering.