Every year, millions of people get the flu vaccine hoping to protect themselves from severe illness. Yet not all flu vaccines work the same way for every person.
A new study has found that while different flu vaccines create similar levels of antibodies, their ability to activate deeper layers of the immune system varies widely depending on the type of vaccine and the age of the person receiving it. These findings could help improve future vaccine recommendations, especially for older adults.
The 2024–2025 flu season was one of the worst in recent years. At least 47 million people became sick, more than 600,000 were hospitalized, and 27,000 died. With numbers like these, understanding how to choose the most effective flu vaccine is more important than ever.
Most vaccine studies look mainly at antibody levels. Antibodies are important because they help block infection and usually keep people from becoming severely ill. But antibodies alone cannot tell the full story. People can still catch the flu even after getting vaccinated, although the illness is usually milder.
To better understand protection, scientists now study something called cellular immunity. This involves B cells and T cells—two types of immune cells that help build long-term memory and strong defense against new infections.
The new research, published in The Journal of Immunology, compared four flu vaccines: Fluzone High-Dose, Fluzone Standard-Dose, Flucelvax, and Fluad. Although all four vaccines raised antibody levels to similar degrees, the way they activated the immune system was very different.
For adults ages 65 to 85, Fluzone High-Dose stood out. It triggered the strongest and most coordinated cellular immune response. This vaccine activated early helper cells, such as circulating T follicular helper cells and antibody‑secreting cells.
These cells are important for helping the immune system build strong, long-lasting protection. As people age, their immune response naturally weakens, so vaccines that can boost cellular immunity are especially valuable.
In younger adults, ages 28 to 60, a different vaccine performed best. Flucelvax, which is made using mammalian cells rather than eggs, created a stronger cellular immune response than the traditional Fluzone Standard-Dose.
Flucelvax more effectively activated T cells that release multiple protective signals at once and produced a more powerful memory B cell response. These memory cells help the body recognize and fight the flu more quickly in the future.
The researchers believe these findings could help guide which vaccines should be recommended for different age groups. The study also highlights the need to look beyond antibody levels when developing new vaccines.
Strong cellular immunity may be the key to designing a universal flu vaccine—one that could protect against many strains for years at a time, instead of requiring a new shot every flu season.
To conduct the study, scientists collected blood samples from volunteers at four different times: before vaccination, then seven, 28, and 90 days afterward. The samples were used to measure how the immune system responded over time. All four vaccines tested were designed to protect against the same four influenza strains: H1N1, H3N2, B Yamagata, and Victoria.
Dr. Ted M. Ross, the senior author of the study and Global Director of Vaccine Development at the Cleveland Clinic, explained that this research provides a clearer picture of how different vaccines work in real people.
He hopes the findings will help build better vaccines in the future. The next steps will involve studying a larger group of patients and identifying the biological markers that predict long-lasting protection.
When reviewing and analyzing the study, the results show a major shift in how we understand flu immunity. Antibodies are only part of the story. Cellular immunity—especially memory B and T cells—may be the key to stronger, longer-lasting protection.
The study also highlights that the best vaccine may depend on your age. Older adults benefit most from high‑dose vaccines that boost weakened immune systems, while younger adults may respond better to cell‑based vaccines like Flucelvax.
This research helps explain why some people still get breakthrough infections and why a universal flu vaccine is so challenging to create. By focusing on cellular immune markers, scientists may finally be able to design vaccines that protect more effectively across different age groups.
Overall, the findings offer new hope for better flu vaccines and a future where severe flu seasons become far less common.
If you care about wellness, please read studies about nutrients that could combat inflammation in older people, and essential foods for healthy aging.
For more health information, please see recent studies about the link between processed foods and chronic diseases, and a simple diet change for a healthier life after 65.
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