Vaccine effectiveness is often evaluated by measuring antibody production, as high antibody levels following vaccination are associated with reduced risk of severe influenza, yet breakthrough infections still occur. Beyond antibodies, the immune system will enlist specialized cells (e.g., T and B cells) to help recognize and eliminate the virus, offering an additional layer of protection that serology tests alone cannot fully capture. Researchers at the Center for Influenza Vaccine Research for High-Risk Populations (CIVR-HRP), led by Principal Investigator Ted Ross, Ph.D., investigated whether cellular immune responses could predict robust, durable immunity. Their findings, published in the Journal of Immunology and highlighted by the American Association of Immunologists (AAI), demonstrated that cellular immunity should be considered in the development of influenza vaccines.
During the 2023-2024 influenza season, adults ages 28-60 and 65-85 received one of four influenza vaccines. Researchers collected blood samples before and after vaccination to measure the concentration of antibodies (called titers) and the presence of immune cells that help defend against the influenza virus. All four vaccines increased antibody titers to a similar degree; however, the cellular immune responses differed across age groups.
In older adults, the Fluzone High-Dose vaccine activated antibody-secreting cells (ASCs) and a subset of T cells called follicular T helper cells (Tfh). Increasing ASCs and Tfhs enhances the production of antibodies, which may allow the immune system of this high-risk age group to more quickly recognize and respond to infection. In younger adults, the Flucelvax vaccine triggered a more diverse response, expanding several subsets of T cells that released cytokines and initiated strain-specific responses. This type of response provided younger adults with broader protection against different types of flu strains.
These findings underscore the importance of incorporating cellular immune markers into vaccine development, particularly to enhance protection for high-risk groups like older adults. The Ross lab plans to continue research on long-term immune memory and identify biomarkers that could improve future influenza vaccines. To learn more about this study, check out the publication and AAI’s article highlighting this research.