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Stanford Medicine Researchers Aim to Enhance Seasonal Flu Vaccine Effectiveness and Combat Future Pandemics
In a groundbreaking study published in Science, scientists at Stanford Medicine have unveiled a novel approach to improving the effectiveness of seasonal flu vaccines. Their innovation not only bolsters the immune system’s response to current flu strains but also holds promise for protecting against new variants with pandemic potential.
The team, led by Dr. Mark Davis and Dr. Vamsee Mallajosyula, has developed a method to overcome the immune system’s natural biases, which often limit the efficacy of traditional flu vaccines. The findings were validated using human tonsil organoids—laboratory-grown tissue models derived from tonsil cells.
The Problem with Current Flu Vaccines
Each year, the influenza virus causes hundreds of thousands of deaths and millions of hospitalizations worldwide. Current flu vaccines aim to protect against four major circulating subtypes of the virus by including versions of the hemagglutinin protein, a molecular hook the virus uses to invade cells. However, vaccine effectiveness often falls short, ranging between 20% and 80% in recent years.
“Many vaccinated individuals fail to produce strong antibody responses to all four subtypes,” explained Dr. Davis, a professor of microbiology and immunology. “Most people develop robust immunity to only one subtype.”
This uneven immune response—known as “subtype bias”—is influenced more by genetic factors than by prior flu exposure, according to the study. The researchers sought to address this bias and ensure the immune system targets all four subtypes equally.
A Novel Solution
The researchers designed a vaccine that chemically links all four hemagglutinin proteins on a molecular scaffolding, compelling the immune system to recognize all subtypes. This innovative approach forces immune cells, specifically B cells, to interact with all four antigens, rather than just the one they are predisposed to respond to.
“Think of it as making B cells eat their broccoli,” said Davis. “By stitching the antigens together, we ensure the immune system pays attention to all subtypes, significantly enhancing the response.”
This method activates helper T cells, which play a crucial role in stimulating antibody production. The result is a robust immune defense against all included influenza subtypes.
Testing and Future Potential
The vaccine was tested using human tonsil organoids, miniaturized models of lymph node tissue, which mimic the body’s immune response. The tests demonstrated strong antibody responses to all four flu subtypes. Additionally, the team included a fifth antigen representing the avian flu hemagglutinin, showing a marked improvement in antibody production against this potential pandemic threat.
“Overcoming subtype bias in this way can lead to a much more effective influenza vaccine,” Davis said. “This approach could also be extended to strains responsible for bird flu, which is a looming pandemic risk.”
Implications and Next Steps
The new vaccine design has significant implications for public health. By broadening immune responses to seasonal flu vaccines and preemptively addressing pandemic threats, this technology could save millions of lives.
Stanford has filed a patent for the coupled-antigen methodology, and further research is underway to move the vaccine toward clinical trials. Researchers from the University of Cincinnati College of Medicine also contributed to the study.
“This represents a major step forward in influenza vaccine development,” Davis said. “Our method not only enhances protection against current strains but prepares us for what could be the next global health crisis.”
Reference
Mallajosyula, V. et al. Coupling antigens from multiple subtypes of influenza can broaden antibody and T cell responses. Science (2024). DOI: 10.1126/science.adi2396.
