Vaccines: They’re even more important than you think

Vaccines work, actually. But that’s not all. Depending on the specific vaccine we’re talking about, that jab might also prevent cancer, heal herpes lesions, help you keep most of your marbles, prevent your kids from dying in early childhood, improve your skin and so much more. These surprising bonuses that can come with vaccination, called beneficial non-specific effects, are common, but not widely understood. In fact, no one knew about them until relatively recently — and when researchers first discovered all this, no one believed them at first.

Before we look at that, let’s consider just how good these non-specific effects can get. Well, the Shingrix (or Zoster vaccine recombinant) vaccine, which is recommended for all adults in later middle age, prevents up to 95 percent of shingles cases. But that’s not all. It also reduces your risk of dementia, with a 20 percent relative risk reduction over seven years. (Shingles is the long-term result of a childhood chicken pox infection, which can hide inside you for decades before re-emerging in notoriously painful fashion.)

Emily Martin, a professor of epidemiology at the University of Michigan, told Salon in a video interview that certain viruses, like the herpes group — which includes the chicken pox virus and the one that causes cold sores, as well as genital herpes — “are notorious for these reactivation and latency patterns, and  changing your health status over the long term based on how much they’re around and active in your body.” It seems that the Shingrix vaccine’s remarkable effect on rates of dementia in older adults is the result of preventing some of those health status changes.

“What the shingles vaccine does is it dampens reactivations of latent viruses in a way that may be protecting other parts of your body,” Martin said. Including, it seems, the brain.

The measles, mumps and rubella or MMR vaccine protects children against those three diseases, of course. (Two doses are 97 percent effective against measles, for example). But that’s not all. It also reduces your child’s all-cause mortality — that is, their risk of dying of any cause, for years.

Oral polio vaccine prevents — surprise! — polio. But that’s not all. Vaccinating a newborn baby within its first two days reduces their risk of dying in their first year by 10 to 62 percent, while also reducing the risk of flu, COVID-19, bacterial diarrhea and otitis media, among other infections, studies have shown.

Vaccines currently in development for Staphylococcus aureus infections, including MRSA, might have the side effect of fighting atopic dermatitis, cellulitis and impetigo — maybe even acne.

We constantly hear from public health officials about how we should get vaccines because it’s good for us, like flossing our teeth. In the U.S., rather obviously, the public health message has gotten more confused of late. We constantly hear from pseudoscience grifters and bleach-drinking advocates that we shouldn’t get vaccines because, well, because of a bunch of hooey. So why isn’t anyone telling us about these remarkable side effects of vaccination? If you were trying to sell a product that not only keeps you healthy when other people are getting sick with, say, chicken pox, but also prevents you from getting a painful and potentially damaging disease many years later, wouldn’t you want to advertise that? Because that thing would sell like gangbusters.

But the numbers don’t lie. Mind you, this is science we’re talking about, and there’s an important distinction between noticing an association and confirming a causal connection. So what’s the cause? By what mechanism do vaccines do so much unexpected good?

There are “basically two ways” of understanding these “off-target effects,” Martin said. “One way of looking at it is that the disease the vaccine is preventing is actually causing a wider range of illnesses and issues than we ever realized before we started vaccinating.” she explained. Influenza, which can cause falls and cognitive status issues in older people during acute infection and recovery, offers a classic example.

“But then, if you look at something like measles,” Martin continued, “those other effects are giant.” Measles is distinctive in that it essentially goes into a person’s system and wipes out the T-cells — a vital part of the immune response — gained during previous infections of other kinds. “Any of the lived experience that you’ve had to build up antibodies against infection then gets wiped out by the measles virus. When you recover from a live measles infection … you’ve just lost all of your immunity. It’ll be like you’re a kid in day care for the first time. So you’re going to be encountering all of these diseases with very little prior immunity.”

Part of the beneficial non-specific effect of measles vaccination, then, derives from preventing a disease whose health impacts are more serious and long-term than scientists originally understood. But there’s a further effect, believed to relate to another phenomenon called trained immunity. That’s what happens when activating an organism’s innate or built-in immunity can result in a later revved-up response to a new immune challenge.

Studies of the effects of various vaccines, Martin said, suggest that the “mild, low-level replication” of a pathogen — which is how most vaccines work — can result in “training the immune system” to protect you against other diseases. Peter Aaby, a Danish anthropologist, discovered the beneficial non-specific effects of vaccines while working in the West African nation of Guinea-Bissau after it gained independence in the 1970s. As in many other poor countries, Guinea-Bissau’s extremely high child mortality, which meant more than half of all children died before age 5, was attributed by mostly Western scientists and policymakers to malnutrition. But when Aaby’s team conducted a survey of 1,200 children, they found that malnourishment was virtually nonexistent. Just after that survey was completed, a severe measles epidemic swept the area, killing one-fourth of all children.

So malnutrition no longer made sense as the “explanation of severe child mortality,” Aaby told Salon in a video interview. “The stunning thing was, there was no relationship. The nutritional status of the children who died of measles was not different from those who survived.”

But he had a hard time getting the Swedish research organization that had hired him, or other medical authorities who reviewed his work, to address the implications of the data. He eventually tested a new hypothesis: It wasn’t nutritional status that determined how bad a case of measles was, but rather how intensely a child had been exposed to the virus.

Those most likely to die, Aaby found, were “the children who are infected inside the home.” When many children lived under the same roof, he explained, they were likely to be exposed to far greater doses of the virus. “That turned out to be by far the strongest explanation of measles mortality,” he said. “I have also subsequently shown that the same pattern applies not just to measles, but [also] for chicken pox, RSV, polio and whooping cough.”

Aaby’s team then went door to door providing measles vaccinations, and a few years later he received a follow-up report, describing what happened to children who had been involved in the study and subsequent ones carried out in rural areas. “I got the idea that maybe measles vaccine had an impact on child survival,” he said. And sure enough, “nearly every time that someone had died [of any cause], they had not been vaccinated.”

Later studies from several countries with data on childhood mortality before and after introduction of the measles vaccine likewise showed a minimum 50% reduction in mortality among children under age 5 — “an unbelievable effect,” as Aaby put it. Children who had previously survived a measles infection had even lower risks of mortality: It’s fair to say that what didn’t kill them did indeed make them stronger, but at a terrible risk, since a quarter of measles-infected children did not survive.

Other vaccines were likewise shown to reduce childhood mortality, without the risks associated with infection, and to an astonishing degree: the BCG vaccine (against tuberculosis) did so by 45%, for example. Aaby’s findings  were initially dismissed, since he was an anthropologist with no medical credentials  (he now has a PhD in medicine), but no longer. In 2016 the WHO noted the otherwise inexplicable effects of BCG and measles vaccines on childhood mortality, while in 2020 the widely-respected journal Nature included non-specific effects in a list of “milestones in vaccines.”

“Child mortality under age 5 has declined by 86 percent, and there is no way you can explain it by controlling measles and whooping cough and tuberculosis,” Aaby emphasized to Salon. “It’s the immune stimulation that we have provided” through vaccination.

As with the protection vaccines provide against a specific pathogen — we need boosters for COVID-19 because the vaccine’s effects wane over time — this enhanced general immune protection may last for just a few months or endure for years, as with the effect of measles vaccination on overall health. Early findings show that existing COVID vaccines may also offer beneficial non-specific effects in similar fashion, as Aaby suggests in a PowerPoint presentation he shared with Salon, by revving up our immune systems against other pathogens.

None of this amounts to saying that vaccines have no risks, or even that their non-specific effects are always beneficial. Aaby found, for example, that what’s known as the high-titer measles vaccine, when given to very young children, was later associated with increased mortality for girls, a finding of sex differences in immune response that has been seen with other vaccines as well. (That specific vaccine is no longer in use.)

Further research revealed that it was the sequence in which vaccines were administered, not the vaccines themselves, that was responsible for higher mortality. Changing the sequence of vaccines, usually by giving live vaccines before non-live ones, maximizes the beneficial effect and removes that additional risk for girls, apparently by programming the innate immune system in a better way. Aaby is now testing whether combining live and non-live vaccines may reduce negative effects while maintaining beneficial effects, both the specific protection against a given infection and the non-specific strengthening of the immune system.

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It’s essential to evaluate the benefits and risks of any vaccine carefully, of course. But too often, public attention is fixated on rare and unlikely negative side effects when the overall protection offered by a vaccine far outweighs any statistical risk. Unless you are a person with known risk factors involving bad outcomes, you’re almost certainly at greater risk by not getting a given vaccine. Epidemiologists and public health researchers are supposed to crunch the numbers and figure these things out, and to adjust recommendations as new findings come in, especially recommendations about what vaccines children need, and when.

Like many experts in the field, Martin is concerned that HHS Secretary Robert F. Kennedy Jr.’s recent dismissal of the entire CDC panel of vaccine experts who do that, and their replacement with known vaccine “skeptics” or outright opponents, puts that at risk.

“I worry what data they are going to use,” Martin said. “if they are not acknowledging the data that’s there and being generated. It is ready for them to review right now. This is an ongoing process that we’re always iterating on, every year, putting out vaccine data” to guide policy recommendations.

High child mortality was taken for granted for centuries. So what happened? In a word, vaccines happened. Anyone who visits an older cemetery anywhere in North America is startled to see the large numbers of tombstones inscribed with the names of infants and young children. Such deaths are relatively rare on our continent today, but Aaby’s work suggests that this dramatic change is not purely due to the prevention of the specific diseases targeted by vaccines.

More recently, he contends, the “enormous reduction we’ve had in [child] mortality in low-income countries in the last 30 or 40 years” can only be explained by the non-specific effects he has documented.

Aaby and his colleagues have followed populations before and after the oral polio vaccine campaigns that began in 1995 and ended in roughly 2015 in various low-income countries such as Guinea-Bissau, Ghana, Bangladesh and Uganda. They determined that childhood mortality overall was roughly 25% lower after the campaign than before. Add to that similar effects from BCG and measles vaccination, and we have, Aaby says, an explanation for the dramatic decline in childhood mortality in many such countries.

One major reason why the U.S. and Western Europe have seen dramatic population increase over the last 200-plus years, Aaby says, is the introduction of the smallpox vaccine in 1800. That wasn’t just that vaccine prevented one specific and often deadly disease, he argues, but because of the vaccine’s overall effect on immune systems.

“There are a lot of things that we’ve forgotten to say” to vaccine-hesitant parents concerned about rare negative effects, said Martin, largely “because measles infection in the United States has been so incredibly rare for the last 30 years.” In other words, at a cultural level we have simply forgotten how common, and how serious, the long-term damage  from exposure to measles and other diseases used to be.

“I think people in other countries who have had endemic measles understand that more acutely than we do,” Martin said. In many such countries, people have high confidence in vaccination despite less reliable access to vaccines, and the reverse is also true, with people in higher-income countries expressing greater vaccine hesitancy.

Indeed, there’s evidence to suggest it may have been a mistake to stop administering the smallpox vaccine after the total elimination of smallpox, or to end the BCG vaccine as tuberculosis infection became rare.

A large Danish study compared children who received the BCG and smallpox vaccines to a cohort that did not. Over nearly 40 years, researchers have found that those who received either vaccine as children had significantly lower risks of dying of natural causes — not just in childhood but clear into their 40s, which was as far as the data followed them. Just because certain diseases are eliminated, Aaby argues, is not necessarily a good reason to remove the relevant vaccines.

Given these almost magical-seeming but real and meaningful effects of vaccines, Martin was dismayed to see experts like the highly qualified and vetted CDC vaccine panel members dismissed by Kennedy and accused, without evidence, of conflicts of interest. “This is work that people are doing because they think it’s important,” she said. “They’re not getting any financial benefit. It was jarring to see it swapped out so quickly like that.”