This discovery could make vaccines more effective for older adults
Ageing weakens vaccine responses, but new insights into the mechanisms could help strengthen immune protection for older adults.
- 3 November 2025
- 3 min read
- by Linda Geddes
Scientists have long puzzled over why vaccines don’t work as well in older adults. Now they think they may know why: immune T cells undergo profound and specific changes as we age, reshaping how our bodies respond to vaccines and pathogens.
The findings, published in Nature, could eventually aid the design of more effective vaccines, researchers say.
Why do older people mount weaker immune responses?
For years, scientists have known that older adults don’t respond to vaccines as well as younger people – but the biological reasons have been difficult to pin down. One leading theory blames chronic low-grade inflammation for the decline. Another is that constant immune stimulation from persistent viruses such as cytomegalovirus (CMV) that remain in the body for life, may gradually reshape how the immune system works.
How old age affects our immune responses
Older adults’ T cells gradually shift into a state that weakens their ability to instruct antibody-producing B cells, weakening their responses to vaccines.
These changes appear to happen even without chronic inflammation or lifelong viral infections: ageing itself rewires the immune system.
The findings could help scientists design more effective vaccines for older adults, predict individual vaccine responses and develop therapies to rejuvenate immune cells.
However, most previous studies have been small, focused on only a handful of immune cell types, and included people with underlying health problems – making it difficult to disentangle the effects of disease from healthy ageing.
To investigate, Dr Claire Gustafson at the Allen Institute for Immunology in Seattle, US, and colleagues closely monitored the immune systems of 96 healthy adults aged 25–65 for two years, sampling their blood repeatedly – including before and after seasonal flu vaccinations. Using cutting edge techniques such as single-cell RNA sequencing, proteomics and spectral flow cytometry, they charted how 71 different types of immune cells shifted with age, and in response to vaccination or chronic virus exposure. They then validated these patterns in a larger cross-section of more than 300 healthy adults up to age 90.
The study found that the biggest age-related changes happened in T cells – especially a type of T cell that helps to “train” white blood cells called B cells to produce antibodies in response to viruses and vaccines. The T cells appeared to shift to a different operating mode as people aged, altering how they responded to threats and directly impacting B cells’ ability to generate strong antibody responses.
This could mean that even if a vaccine is well-matched to a virus, older immune systems may struggle to produce strong antibodies because their T cells are no longer providing clear instructions to their B cells.
Surprisingly, these shifts didn’t appear to be driven by chronic inflammation or lingering viral infections such as cytomegalovirus.
“We were surprised that inflammation is not driving healthy aging. We think inflammation is driven by something independent from just the age of a person,” said Gustafson, adding that other research also supported the idea that inflammation and ageing don’t necessarily go hand in hand.
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How could this lead to better vaccines?
The findings could eventually pave the way for tests to predict how well someone will respond to a vaccine based on their individual immune profile. They could also aid the design of vaccines that are better tailored to ageing immune systems, or treatments to rejuvenate aging immune cells.
More broadly, the findings provide a window into how the immune system shifts as we get older, and how those changes could influence our susceptibility to infections and age-related disease.
“My hope is that [our dataset] will be used for a long time to enable other researchers to look more deeply and find more insights into human immunity,” Gustafson said.
