A new, nanoparticle vaccine could one day grant patients immunity to the flu with fewer trips to the doctor and without health officials correctly guessing which flu strains will become dominant each year.
Mice given the vaccine, developed at University of Michigan Engineering, were successfully protected against three different strains of flu, according to a study to be presented Aug. 24 at the American Chemical Society’s fall 2026 conference. The team achieved the broader protection by targeting a virus protein that mutates more slowly than the main proteins our bodies recognize on inactivated flu viruses. Current flu vaccines must include a mix of three or four flu variants to achieve the same level of protection, and even then, they are only 30%-60% effective.
“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,” said Fei Wen, U-M professor of chemical engineering and the corresponding author of the study, which was partially funded by a National Science Foundation CAREER Award. “Eventually, with enough effort and research, we believe that you might need one shot to be protected for life.”
Antibodies that match more viruses
When we get flu shots, our immune systems confront deactivated flu viruses injected into our arms. The main protein they detect is hemagglutinin, which makes up 80% of the virus’s surface. But the immunity is temporary because hemagglutinin is prone to mutation, with 19 versions currently in circulation and new variants emerging every few years.
Because of the variability in hemagglutinin, the World Health Organization and the Centers for Disease Control and Prevention monitor which strains are spreading, so vaccine manufacturers can include them in the latest vaccines. But if a new strain emerges, the vaccines may not work as expected. In 2025, a new flu variant, called subclade K, emerged that contributed to one of the United States’ more severe flu seasons in recent years. Over 320,000 flu patients were admitted to the hospital and more than 10,000 died, according to CDC data. The swine flu pandemic of 2009 was also caused by a new flu variant.
Instead of leaving our immune systems to choose which proteins to react to on an inactivated virus, the new vaccine provides one option: the M2 protein. This flu protein is less likely to mutate because changes can make it harder for the virus to replicate. M2 is very similar across influenza A viruses, including seasonal flu, swine flu and bird flu. However, our immune systems don’t naturally target M2 because there is much more hemagglutinin on viruses.
New vaccine, new manufacturing method
The new vaccine is made of particles that are roughly the same shape and size as flu viruses but are covered in M2 protein.
These virus-like particles are made using baker’s yeast. The researchers genetically modified ordinary yeast to make large amounts of the M2 protein. After incubating the yeast in a nutrient-rich liquid, the researchers treated the microbes with mild chemicals to gently remove their rigid cell walls. When the outer wall is removed, the yeast will bud off the virus-like particles, which the researchers collect.
With their new manufacturing method, the researchers can produce a large amount of flu vaccine in a month. In contrast, conventional flu vaccines made in chicken eggs require six months.
If a new M2 strain does emerge out of nowhere, we’ll be able to quickly edit the vaccine. Our method could improve pandemic response time.”
Trang Hoang, U-M doctoral student in chemical engineering and first author of the study
The team has licensed their technology to Esperovax, with the help of Innovation Partnerships, to develop an oral vaccine. But there is still a lot of work to be done before it’s ready for people. The researchers’ next step is to measure how long the M2-vaccinated mice remain immune to flu.
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