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Stanford Medicine researchers develop a game-changing method for influenza vaccination that could protect against all major flu subtypes — and emerging pandemic threats.
Stanford Medicine scientists have unveiled a groundbreaking method to significantly improve seasonal flu vaccines, potentially offering protection against all four major flu subtypes and even providing a shield against future pandemic strains, such as bird flu. Their innovative approach, which utilizes a combined antigen methodology, was demonstrated through lab tests using human tonsil organoids and published in Science on December 19, 2024.
Each year, influenza causes widespread illness, hospitalizations, and deaths, with hundreds of thousands of people worldwide succumbing to the virus. While the seasonal flu vaccine helps prevent the worst effects of influenza by preparing the immune system, it has long struggled with inconsistent efficacy, ranging from 20% to 80%. This is largely due to the body’s tendency to mount a strong immune response to just one subtype of the virus, leaving people vulnerable to other circulating strains.
Unlocking the Mystery of Immune Response
The flu vaccine works by priming the immune system to recognize specific viral antigens, which are protein molecules that help the virus latch onto cells. Hemagglutinin, the key protein on the surface of the influenza virus, is the primary target of current flu vaccines. However, existing vaccines struggle to induce a robust response to all four subtypes of the virus, which results in varying protection across individuals.
Dr. Mark Davis, professor of microbiology and immunology at Stanford, and his team have uncovered the reason behind this inconsistent immune response. Their research suggests that the immune system’s tendency to prioritize the first flu strain it encounters — a phenomenon known as “original antigenic sin” — may explain why many people only develop strong immunity to one subtype. The team discovered, however, that genetic factors, rather than prior flu exposure, largely determine which subtype receives preferential attention from the immune system.
A Revolutionary Vaccine Design
To overcome this issue, Davis and his colleague, Dr. Vamsee Mallajosyula, designed a revolutionary vaccine that forces the immune system to respond to all four influenza subtypes equally. Their approach involves chemically linking the four versions of hemagglutinin — the principal flu antigen — onto a single molecular scaffold. This unique configuration ensures that immune cells (B cells) recognize and process all four hemagglutinin types, even though they would typically focus on only one.
The new vaccine approach has shown promising results in laboratory tests using cultured human tonsil organoids, which mimic the body’s lymphatic system. When exposed to this combined antigen vaccine, the organoids produced strong immune responses to all four common flu subtypes, leading to the production of antibodies capable of neutralizing the virus.
Potential for Pandemic Protection
The researchers further extended their work by testing the vaccine’s ability to generate an immune response against avian or “bird flu” — a viral strain that poses a serious pandemic risk. While bird flu has yet to be easily transmitted between humans, its ability to mutate into a more infectious form makes it a major concern. The new vaccine demonstrated its potential to significantly enhance antibody responses against bird flu when combined with the four seasonal flu antigens.
By incorporating this fifth antigen, the modified vaccine showed a far more robust defense against the avian virus compared to traditional methods. According to Davis, this approach could offer a powerful tool in preventing the next global influenza pandemic.
The Road Ahead
This breakthrough could represent a major leap forward in the fight against influenza, improving both seasonal protection and safeguarding against potential pandemic strains. As the flu virus continues to evolve, the ability to develop a vaccine that can target multiple subtypes — and even emerging threats like bird flu — is crucial to global health.
For more information on this cutting-edge research, see Unlocking the Genetic Code to Supercharge Flu Vaccines.
Reference:
“Coupling antigens from multiple subtypes of influenza can broaden antibody and T cell responses” by Vamsee Mallajosyula, et al., Science, December 19, 2024. DOI: 10.1126/science.adi2396.
