Vaccines remain one of the best ways to protect people from infectious diseases, but they do not work equally well in everyone.
Older adults often produce weaker immune responses after vaccination because the immune system gradually loses strength with age. Researchers now believe that slowing this process of immune aging could improve vaccine protection.
Scientists at NDORMS have investigated whether spermidine, a natural compound found inside human cells and in certain foods, might help older immune systems respond more effectively to vaccination. Their findings were published in Aging Cell.
During the COVID-19 pandemic, older adults accounted for the vast majority of deaths. Although vaccines greatly reduced severe illness, many older people generated fewer protective antibodies and weaker T-cell responses than younger adults. Understanding why this happens has become an important goal for researchers.
The team recruited 40 healthy volunteers over the age of 65 who had already received three COVID-19 vaccine doses. Participants took either a daily spermidine supplement or a placebo for 13 weeks. Because the trial was randomized and double-blinded, neither participants nor researchers knew who received the active treatment until the study was completed.
Overall, the supplement proved safe. More importantly, researchers identified a subgroup of participants who had responded very poorly to vaccination despite receiving three doses. Their immune cells showed evidence of biological aging, including DNA damage and cellular senescence, meaning the cells had largely stopped functioning normally.
In these poorer responders, spermidine supplementation was associated with stronger antibody production, healthier B-cell responses, and improved ability to neutralize different coronavirus variants. The researchers also found evidence that spermidine stimulated autophagy, the natural process cells use to recycle damaged components and maintain healthy function.
These findings suggest that some cases of poor vaccine response may result from accelerated aging within immune cells rather than simply chronological age. If future studies confirm this idea, doctors might one day identify people most likely to benefit from therapies that target immune aging.
Despite the exciting results, important questions remain unanswered. The trial involved only 40 participants, making it far too small to determine whether spermidine should become part of routine healthcare. Researchers must also determine whether the same effects occur after influenza vaccines and other routine vaccinations.
Study analysis: The study’s strengths include its randomized placebo-controlled design and its focus on biological mechanisms explaining poor vaccine responses.
Its greatest limitation is the small number of participants, which means larger trials are essential before any clinical recommendations can be made. At present, the findings should be viewed as promising but preliminary.
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Source: NDORMS, University of Oxford.
