Hypothesis links routine vaccines to dementia protection via trained immunity
Researchers led by Justin Devine propose that vaccines for shingles, flu, and BCG could lower dementia risk by training the immune system to prevent neuro-inflammation, moving beyond theories of direct pathogen prevention.
A growing body of epidemiological evidence suggests that routine vaccinations, including those for shingles, influenza, and the Bacillus Calmette-Guérin (BCG) vaccine, are associated with a reduced risk of dementia. While the direct prevention of infections that cause brain inflammation has long been the primary explanation for this link, a new hypothesis published in March in Frontiers in Immunology proposes a different mechanism: trained immunity.
Led by Justin Devine, researchers from Belgium and South Africa argue that vaccines may induce epigenetic reprogramming in the innate immune system. This process, first described in 2011, challenges the historical view that innate immunity is static. Instead, it suggests that exposure to vaccine antigens primes innate immune cells to respond more intensely to generic germ signals upon re-exposure, potentially preventing the neuro-inflammation linked to cognitive decline.
The concept of trained immunity was initially solidified through studies on the BCG vaccine, which is used against tuberculosis and bladder cancer. Research published in the Proceedings of the National Academy of Sciences demonstrated that BCG vaccination induced non-specific trained immunity in both mice and humans, enhancing responses to unrelated pathogens such as Candida albicans and Staphylococcus aureus. A 2023 study further linked the BCG vaccine to a significantly lower risk of dementia, providing a foundation for the current hypothesis.
While the protective effect of the shingles vaccine is often attributed to preventing the reactivation of the varicella-zoster virus, which can trigger brain inflammation, the mechanism for other vaccines remains less clear. Recent data from a large retrospective study published in May indicates that high-dose seasonal flu shots provide greater protection against dementia than standard doses. This dose-dependent response suggests a biological mechanism beyond simple pathogen avoidance, prompting calls for further investigation into trained immunity.
The authors of the March hypothesis note that uncontrolled neuro-inflammation is a key driver of dementia risk. They propose that the epigenetic changes induced by vaccines may help keep both targeted and non-targeted pathogens in check, thereby mitigating inflammatory responses in the brain. Although the idea remains a hypothesis requiring validation, the researchers emphasise that elucidating these mechanisms could open new avenues for promoting healthy ageing and alleviating the global burden of dementia.
