Dec. 11, 2024 — Here’s a thought that may coax you toward getting the flu vaccine: Think of it as a seasonal “buy one, get one free” special. In the case of a flu shot, vaccination can bring more than just one unexpected benefit.
Research shows that immunization against the flu has been linked to a lower risk of Alzheimer’s disease as well as a reduced risk of heart failure and stroke. What’s more, the shingles vaccine may lower the risk of Parkinson’s disease and stave off dementia. The rotavirus vaccine, given routinely to infants, may delay the onset of diabetes. And COVID-19 vaccines and boosters not only reduce the likelihood of getting the disease but also lower the chances of serious heart and blood-vessel complications.
To be sure, Americans are increasingly distrustful of vaccinations. As many as 22% of people surveyed by the Annenberg Public Policy Center at the University of Pennsylvania falsely believed that it’s less dangerous to get COVID-19 than to vaccinate against it. The survey also found that skepticism extended to other vaccines too, such as those for HPV, shingles, pneumonia, and RSV. Gallup polls show, meanwhile, that the numbers of those who consider childhood vaccines as important is down from 64% in 2001 to 40% today.
Yet happy byproducts of vaccinations have been noticed for more than a century, after two French scientists grew tuberculosis bacterium on potatoes cooked in ox bile. The resulting vaccine protected animals, and then humans, from tuberculosis, which killed about 1 in 500 Americans per year in the early 20th century.
The vaccine not only slashed the occurrence of TB, but the scientists found that death rates among vaccinated children were four times lower than those of unvaccinated children. The vaccine may “confer on the organism a special aptitude to resist those other infections,” one of the scientists wrote in 1931. The TB vaccine is rarely given in the United States these days, but advantages keep turning up: A European study found that the tuberculosis vaccine given in childhood may delay the onset of diabetes.
For Americans, here’s what medical history and new research say about the bonuses of vaccines beyond preventing the diseases they target.
When Vaccines Go Above and Beyond
Textbooks usually define vaccines as suspensions aimed at providing immunity against a specific germ, say, the flu virus. Yet science now shows that’s not the whole story. When measles vaccination programs were rolled out in low-income countries, the drops in childhood deaths reached as much as 50%, even though the disease accounted for just 10% of deaths.
In Denmark, a recent study found that flu jabs lowered overall deaths among adults by 18% — an outcome comparable to that of a healthy diet, and which couldn’t be simply explained by fewer cases of flu. These extra effects have been “proven beyond any doubt,” said Christine Stabell Benn, MD, PhD, DMSc, an epidemiologist at the University of Southern Denmark. Researchers call these effects “nonspecific” to separate them from those that the vaccines were originally designed for. In many situations, she said, “the nonspecific effects might be even more important than the specific effects.”
Higher doses may provide even more protection. A recent study in Denmark with over 12,000 participants showed that a dose four times higher than usual cut death rates almost by half compared with the standard dose. What’s more, the effects appeared even before the flu season took off. “We knew we had no flu circulating,” said Tor Biering-Sørensen, MD, PhD, MPH, a cardiology researcher at the University of Copenhagen, Denmark, and the study’s lead author. “Those getting boosted with a higher dose had better protection against several outcomes. It’s not just flu, it’s also the cardiovascular outcomes,” Biering-Sørensen said.
Another study by Biering-Sørensen and his colleagues, which looked at the flu vaccine and cardiovascular disease in almost a quarter million people, found that it reduced the risk of death from stroke by 15% and from cardiovascular disease by 17%. And the more flu shots one gets, the better — at least for preventing heart failure. In one study, people who had accumulated more than three flu shots over the period of the study (which ranged from about two to seven years, depending on the patient), had the lowest risk of cardiovascular death. The reduction was comparable to what you might expect from following the Mediterranean diet.
In another example, the measles-mumps-rubella (MMR) vaccine lowers the risk of various respiratory infections by 18%.
An Old Vaccine’s New Promise
The pioneering work of those two French scientists, Albert Calmette, a medical doctor, and Camille Guérin, a veterinarian, in 1908 continues to pay dividends. Their vaccine is known as BCG, or the Bacillus Calmette-Guérin vaccine. It is the most used vaccine on Earth and makes people more resistant to a plethora of germs other than tuberculosis. Studies show it lowers the risk of sepsis and fatal respiratory infections and protects against the yellow fever virus as well as the human papillomavirus.
New research shows that BCG could help those with autoimmune diseases, too. In one trial, after a BCG vaccination, MRI images of multiple sclerosis patients showed fewer enhancing lesions, a marker of disease activity. In a trial on type 1 diabetes, BCG vaccination helped restore blood sugars to near normal, even in patients who had the disease for years. For Crohn’s disease, some research suggests that BCG vaccination could sustain remission, and a study published in November 2024 showed that tetanus vaccination is linked to a slower progression of Parkinson’s disease.
The use of vaccines to remedy autoimmune disorders or cardiovascular issues remains mostly in the domain of research. But BCG already has a long-proven record as a successful treatment for bladder cancer. Since the 1970s, BCG injected directly into the bladder became the standard of care for early-stage cancer that has not invaded the bladder muscle wall. A 2017 meta-analysis of 39 trials confirmed that the vaccine decreased risk of cancer recurrence and progression.
What’s more, the research on BCG in bladder cancer had a surprising side effect: It revealed that people who received the injection were more likely to keep their minds sharp. In one such study of bladder cancer patients, those who were treated with BCG had a four times lower risk of Alzheimer’s disease than those who didn’t get the vaccine.
Does that mean it was a mistake for countries like the U.S., Finland, the United Kingdom, and others to discontinue universal tuberculosis immunization programs? It’s worth discussion. For instance, rates of dementia tend to be lower in nations with widespread BCG coverage, such as Lithuania, Chile, or Brazil — even accounting for economic differences.
In one recent experiment, compared with people given placebo shots, those given BCG had lower levels of amyloid-beta in the blood — a sticky protein that is a sign of Alzheimer’s disease.
And it’s not just the BCG vaccine that may help us maintain mental fitness: so can Tdap, (the vaccine for tetanus, diphtheria, and pertussis), Shingrix (a shingles vaccine), and the flu vaccine, which according to one 2024 study may lower the risk of vascular dementia by 42% and Alzheimer’s disease by 21%. But BCG appears the best at staving off Alzheimer’s when compared with other vaccines.
How Do Vaccines Confer These Surprise Benefits?
A vaccine is a suspension of dead, weakened, or fragmented germs designed to protect us from specific infectious diseases. To a large extent, it’s a mystery as to how they provide these nonspecific effects. “We are still in such a learning phase,” Stabell Benn said. Yet certain patterns are emerging.
Imagine someone already struggling with diabetes. Then add the flu or shingles. “A viral infection increases the metabolic load on a stretched system,” Biering-Sørensen said. It makes it “harder for the body to cope,” he said. A vaccine can prevent that.
As for cognitive health, research suggests that certain microbes may get inside the brain and trigger dementia. “The growing view in the field is that infection is a likely contributor to the emergence of pathologies such as Alzheimer’s disease,” said Richard Lathe, DSc, a molecular biologist at the University of Edinburgh. Amyloid-beta, the sticky protein that’s a marker of Alzheimer’s disease, is a weapon the body uses to deal with pathogens. It’s “protective against a range of bacteria, fungi, and viruses,” Lathe said. But as the protein collects in the brain, our mental skills suffer. Vaccination, Lathe said, may “boost the immune system,” preventing germs from invading the brain.
Evidence is piling up that vaccination can train the innate immune system, one of the body’s main lines of defense against germs. The innate immune system attacks all intruders, as opposed to the adaptive immune system, which targets specific bacteria or viruses and which is what vaccines are generally designed for. Vaccines may reprogram cells of the innate immune system, such as natural killer cells, so that they respond faster to invaders no matter what they are. This is also how the BCG vaccine helps treat bladder cancer: It boosts the activity of macrophages, the white blood cells that kill germs and cancer cells.
What’s more, research shows that mere hours after a shot, the BCG vaccine can prepare the bone marrow for an emergency response in case of a body-wide infection that’s not necessarily tuberculosis. If bacteria or viruses attack, such vaccine-prepped bone marrow will produce large numbers of neutrophils, one of the first cells to fight an infection.
Not all immunization works equally well, however, and not all people react to the same extent. Even within the BCG vaccine there is considerable variation between batches, with some strains training the innate immune system better than others. For children, whether their mother was vaccinated matters. In one study, newborns of mothers with a BCG scar had an additional 25% lowered risk of death after their own jab, which could not be explained by protection against tuberculosis. A similar effect was found with the measles vaccine.
Considering that live-attenuated vaccines (vaccines that use a live but weakened virus) such as the BCG, or those against measles or smallpox, work particularly well at training the immune system, eradicating certain diseases may come at a cost. Take smallpox. “Everybody was just happy that we could stop that vaccine. But it turns out that paradoxically, we may have actually done something really bad to population health,” Stabell Benn said. Research from Denmark showed that people vaccinated for smallpox had lower long-term risk of death even with the disease wiped out.
Yet there are opportunities here, too. We could, for instance, design next-generation vaccines specifically for their immune-boosting side effects, which could not only lower the burden of cardiovascular disease or dementia, but also better prepare us for future pandemics. “That makes much more sense than trying to look for specific vaccines against everything,” Stabell Benn said.
