Routine vaccines may cut dementia risk—experts have startling hypothesis on how - Ars Technica

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More and more routine vaccines are being linked to lower risks of dementia. Shots against seasonal flu, RSV, tetanus, diphtheria, and pertussis (Tdap), pneumococcal infections, hepatitis A and B, and typhoid have all been linked to lower risks. And one of the strongest connections is from vaccination against shingles, with more data supporting the link still coming in. But as the evidence mounts, scientists continue to puzzle over the pleasant surprise—how are vaccines that target specific pathogens inadvertently shielding our minds from deterioration?

A burgeoning hypothesis offers a brow-raising possibility: The shots may be protecting our noggins by training the part of our immune system that had long been considered untrainable. If the idea holds up, it could generate a deeper understanding of fundamental aspects of our immune systems while opening new avenues to treating or preventing dementia. It could also add another dimension to the benefits of vaccines, which already save millions of lives worldwide.

Trained immunity

It’s well understood how vaccines work generally; they’re designed to prime our immune systems against specific pathogens. Vaccines present either defanged pathogens or distinctive fragments of them to specialized immune cells—namely, T cells and antibody-producing B cells—that can then learn to identify those microbial enemies.

So if such a pathogen stages an attack after immunization, those immune cells will be able to recognize the invaders quickly and destroy them. This process, as intended, engages adaptive immune responses, the part of the immune system known to be trainable. It can learn to target specific threats—and remember those threats, aka immunologic memory.

Then there’s the other part of the immune system, the innate immune responses. These precede adaptive responses, acting as first-line, non-specific defenses against germs and injury. Innate defenses include everything from physical barriers—skin, mucous, gastric acid—to immune cells that can indiscriminately gobble invaders, as well as chemical signals that can swiftly ignite generic inflammation.

For decades, the innate immune response was considered relatively static—not one that evolves or hones itself as new threats are encountered. But that changed in 2011 with the coining of the term “trained immunity” to explain changes documented in innate immune responses from past exposures. Trained immunity occurs when cells involved in innate responses are activated and then primed by generic signals from a germ. Those primed cells acquire and maintain changes that allow them to respond to those germ signals faster and with more intensity the next time they’re encountered.

Specifically, the changes observed in trained immunity are epigenetic. These don’t alter the underlying DNA sequence of the cells but are modifications or chemical tags that alter gene activity. In the case of trained immunity, the changes may involve genes coding for pro-inflammatory signals that make those genes more active when the same germ signal is encountered again. Ultimately, this would lead to a stronger inflammatory response. Similar to adaptive responses, these epigenetic changes stick around afterward, creating another type of immunologic memory.

Quirky vaccines

So how does this connect to vaccines? The concept of trained immunity was solidified by data involving a vaccine—but one that’s far from routine in the US: the quirky Bacillus Calmette-Guérin (BCG) vaccine, which was designed to protect against tuberculosis, caused by the bacterium Mycobacterium tuberculosis, but also used to treat bladder cancer (it’s still unclear how the vaccine works against this cancer).

Nevertheless, in 2012, researchers in the Netherlands conducted an experiment to investigate trained immunity in mice engineered to lack adaptive immune responses—they had no T cells or B cells. The researchers vaccinated the weakened animals with BCG, looking for changes in innate responses, the only responses the mice had.

The researchers found that the shot not only bolstered the rodents’ protective innate responses against M. tuberculosis but also boosted responses against an unrelated yeast pathogen, Candida albicans. Further work suggested similar trained immunity occurred in humans.

In the same study, the researchers examined blood samples from healthy human trial participants before and after immunization with BCG. After...