The world mostly relies on an 80-year-old method for producing flu vaccines from chicken eggs - a slow, costly process that struggles to quickly adapt to new, mutant strains. Now, researchers at the University of Michigan Engineering have developed a process to manufacture flu vaccines in baker's yeast that is fast, inexpensive, and safe. Early results from mouse studies suggest the approach could make the yearly flu shot obsolete by providing long-lasting protection against multiple influenza strains.
The researchers will present their results at the fall meeting of the American Chemical Society (ACS) during the "Undergraduate and Graduate Research in Biochemistry and Chemical Biology" symposium in McCormick Place. ACS Fall 2026 is being held August 23-27.
"It sounds like science fiction, but we're very excited by the potential of this yeast-based vaccine production system." - Fei Wen.
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Despite intense research, a universal flu vaccine that gives broad, long‑lasting protection against multiple strains and subtypes has remained elusive. Most vaccines target hemagglutinin (HA), a viral surface protein that triggers a strong immune response - a prerequisite for effective vaccines. However, HA mutates rapidly, requiring the design of a new vaccine (and another shot in the arm) each year.
Instead, Trang Hoang, a graduate student at the university, targeted a different viral protein: M2, which is essential for producing new viruses. "The influenza M2 protein is far less prone to mutation than HA," explains Hoang. "M2 has remained relatively conserved since the 1918 flu pandemic and shows high sequence conservation across human, swine, and avian influenza A strains."
"Sequence conservation's very important because pandemics usually start when strains jump from one host to another," adds Fei Wen, a Professor of Chemical Engineering and Hoang's advisor. Previously, researchers focused on HA for vaccine development rather than M2 because of HA's stronger antibody response. But by targeting a highly conserved viral protein such as M2, the researchers hoped the resulting vaccine would provide broad protection that lasts longer than a year, perhaps even a lifetime.
Fei Wen
Along with targeting M2, Wen and Hoang aimed to develop a more cost‑effective, rapid system for manufacturing large amounts of the new vaccine that doesn't require incubation in chicken eggs. Their approach uses baker's yeast (Saccharomyces cerevisiae) to produce virus-like particles (VLPs) that display the M2 protein on their surface. VLPs mimic the virus' size, shape, and behavior but do not contain the genetic material that causes infection. The researchers reasoned that including high amounts of M2 on VLPs could increase the viral protein's ability to trigger an immune response.
Hoang transformed ordinary yeast into VLP factories by editing the yeast genome to make large amounts of the influenza M2 protein. After incubating the yeast in a nutrient-rich liquid, she treated it with mild reagents to gently remove the yeast's rigid cell wall - an essential step for allowing VLPs to bud from the yeast's plasma membrane. Then, Hoang separated and purified the M2 VLPs from the yeast by centrifugation.
Hoang vaccinated 18 mice with these purified M2 VLPs to test whether they could stimulate a strong immune response. Blood serum collected from the vaccinated mice contained abundant antibodies against M2 from five influenza strains. She then exposed the VLP‑vaccinated mice to three of the different influenza strains, observing 100% protection from infection. These results indicated that the new vaccine activated the immune system and protected mice against multiple strains of influenza.
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Although the findings in mice are promising, work still needs to be done before the universal flu vaccine is ready for human trials, the researchers say. For one, they plan to investigate how long M2 VLP-induced immunity lasts in mice. "I would definitely anticipate that the M2 vaccine provides broader and longer protection than the current HA-focused vaccines," says Wen. "Can it be even longer than that, like once in a lifetime? Possibly, or maybe people will need a booster when they get older." Wen also wants to explore new vaccine designs for people with weak immune responses.
The team has licensed the technology to a company developing yeast systems to produce oral vaccines. Wen speculates that someday, engineered yeast strains could be "brewed" as oral vaccines for influenza and other diseases. "It sounds like science fiction, but we're very excited by the potential of this yeast-based vaccine production system," she says.
The research was funded by the College of Engineering at the University of Michigan and the National Science Foundation Faculty Early Career Development Program (CAREER) grant.
