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Breakthrough efforts aim to end annual flu shot updates
Researchers worldwide are advancing experimental vaccines designed to provide broader, longer-lasting protection against influenza, potentially eliminating the need for yearly immunizations.
The flu's relentless evolution
Influenza infects approximately one billion people globally each year, causing fever, fatigue, and respiratory symptoms that can last over a week. The virus claims between 290,000 and 650,000 lives annually, according to health authorities.
The virus's ability to mutate rapidly makes it a moving target for the immune system. Current seasonal vaccines, which typically achieve up to 60% effectiveness, must be reformulated annually to match circulating strains. Mismatches can reduce protection significantly.
"Flu varies constantly. It's a never-ending challenge to stay ahead," said Julie Ostrowsky, a research scientist at the University of Minnesota's Center for Infectious Disease Research and Policy.
Julie Ostrowsky
Targeting the virus's weak spots
Scientists are exploring multiple strategies to create a universal flu vaccine. One approach focuses on the stable regions of the virus's surface proteins, such as haemagglutinin, which mutates less frequently than other parts.
Florian Krammer, a researcher at the Icahn School of Medicine at Mount Sinai, likens haemagglutinin to an ice cream cone: while the "flavor" (variable region) changes often, the "cone" (stable region) remains consistent. His team's vaccine candidate trains the immune system to target the cone, generating a broader response.
In 2020, Krammer's team demonstrated this technique's potential in early human trials. Further refinements are underway, with additional testing planned for 2026.
Overwhelming the immune system
Another strategy involves exposing the immune system to thousands of haemagglutinin variants simultaneously. Nicholas Heaton, a professor at Duke University, developed a vaccine candidate using over 80,000 variations of the protein. The approach forces the immune system to focus on the virus's unchanging components.
Preliminary results from a 2024 study showed promise, though human trials have not yet begun.
Alternative approaches and AI innovations
Researchers at Stanford University recently unveiled a nasal spray designed to activate immune cells in the lungs. Tested in mice, the spray reduced pathogen levels by 100- to 1,000-fold and lasted three months. Human trials are pending.
Other teams are targeting neuraminidase, another viral protein that mutates more slowly than haemagglutinin, or stimulating T cells for long-term immunity. Meanwhile, AI tools are being developed to improve strain selection for seasonal vaccines. Regina Barzilay at MIT created an AI system that analyzes influenza data to optimize vaccine formulations, potentially outperforming current methods.
Challenges and cautious optimism
Despite progress, a truly universal flu vaccine remains years away. Krammer estimates that protecting against all influenza A and B strains-including pandemic and zoonotic threats-would require significant time, funding, and sustained commitment.
Heaton tempers expectations, noting that even a broadly protective vaccine may not cover every strain. However, incremental improvements, such as high-dose vaccines for older adults, are already enhancing protection.
"I wouldn't be surprised if we have an improved influenza vaccine within the next five to ten years," Heaton said.
Nicholas Heaton
