Study reveals that flu vaccine performance varies by age

New research comparing four different flu vaccines found that the ability of the vaccines to activate cells of the immune system that help to protect against infection varied greatly depending on the vaccine type and age of the patient. Researchers say these findings have the potential to guide vaccine recommendations, especially for older adults.

The 2024-2025 flu season was considered highly severe, causing at least 47 million illnesses, 610,000 hospitalizations, and 27,000 deaths. A new study, published in The Journal of Immunology, found that while all four seasonal influenza vaccines produced similar antibody levels, their ability to activate cellular immunity varied greatly depending on the vaccine type and age group.

Antibody levels are what scientists usually look at to determine if a vaccine produces an immune response. High antibody levels in response to the flu vaccine do protect a person from severe influenza. However, high antibody levels do not guarantee complete immunity, and people may still experience breakthrough infections, though less severe than if unvaccinated. 

To better understand the full picture of immunity, the researchers investigated different measures of cellular immunity, which can predict robust, long-lasting immunity better than measuring antibodies alone.

In this study, the researchers investigated four different flu vaccines: Fluzone High-Dose, Fluzone Standard-Dose, Flucelvax, and Fluad.

Fluzone High-Dose vaccine generated the strongest and most coordinated B- and T-cell immune responses in older adults (ages 65-85). This included early activation of types of immune cells called circulating T follicular helper cells and antibody-secreting cells, which help the immune system build long-term memory.

In younger adults (ages 28-60), Flucelvax, the mammalian cell-based vaccine, outperformed Fluzone Standard-Dose, the standard egg-based vaccine. Flucelvax better induced immune cells responsible for orchestrating complex immune responses (multifunctional cytokine-secreting CD4⁺ T cells) and a more robust memory B cell response.

“Our findings provide a more comprehensive understanding of how different influenza vaccines stimulate the cellular component of the immune system across various age groups which can help guide vaccine recommendations,” said Dr. Ted M. Ross, Global Director of Vaccine Development at the Cleveland Clinic and senior author of the study.

“Ultimately, this research could guide the development of next-generation or universal influenza vaccines that offer broader and longer-lasting protection as our results emphasize the importance of including cellular immune markers in vaccine evaluation and design,” continued Dr. Ross.

Researchers are keen to develop a universal flu vaccine that provides broad, long-lasting immunity to all or most influenza strains, as it could reduce the need for annual flu vaccines.

Patients were recruited for the study between September 2023 and March 2024. Blood samples were collected from all patients before vaccination and 7, 28, and 90 days after vaccination. Samples from across the different time points were analyzed to measure immune responses. All vaccines provided patients immunity to four influenza strains: H1N1, H3N2, B Yamagata, and Victoria.

Dr. Ross and his team plan to expand this research to a larger group of patients and investigate how vaccine formulation impacts long-term immune memory. They also plan identify biomarkers of durable immune protection that could guide the design of improved influenza vaccines.

The research article is available in The Journal of Immunology website, or you can read more in AAI News & Views.

Requests for interviews with authors, The Journal of Immunology or the American Association of Immunologists can be made to kpalmer@aai.org.

About The American Association of Immunologists

The American Association of Immunologists (AAI) is one of the world’s largest organizations of immunologists and scientists in related disciplines. Our mission is to improve global health and well-being by advancing immunology and elevating public understanding of the immune system. AAI members are responsible for some of the most significant biomedical discoveries of the past century, including the development of life-saving cancer immunotherapies, antibody therapies, transplant technologies, and vaccines. We support scientists across the field of immunology through knowledge dissemination, community building, advocacy, and public outreach.

About The Journal of Immunology

The Journal of Immunology (The JI) publishes peer-reviewed manuscripts describing novel findings in all areas of experimental immunology, including both basic and clinical studies. The JI is owned by the American Association of Immunologists and published in partnership with Oxford University Press.

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