The unknown mysterious efficacy and the anti-disease principle of vaccines

Vaccines have provided covert, unexpected protection to humans for more than a century. Now, scientists are working to find out how the vaccine does it.

Peter Aaby shook his head as if he still couldn’t believe it. “This is just the beginning – very strange things have happened,” he said.

Today, Abiy talks to me via Skype in his country, Denmark. He has spent most of the past 40 years in Guinea-Bissau. Guinea-Bissau is a small, impoverished West African country that has been colonized in the past, has been in constant trouble, and, more recently, has seen frequent coups. He moved there in 1978 and established a charity, the Bandim Health Project.

There was no national program for measles vaccination at the time, so after a devastating outbreak, the agency decided to focus its efforts on vaccinating local children.

About a year after being vaccinated, they made a startling discovery: Those who had been vaccinated against measles had a 50 percent lower mortality rate than those who had not. “It was shocking,” Abbie said, but not for the reasons that first thought.

In fact, measles is responsible for less than half the child mortality rate elsewhere in Guinea. Based on the proportion of people who initially died from the disease, the vaccine should be far less effective than it used to be. These numbers do not add up ” We asked ourselves, how is this done?” Abiy said.

Large trials found that vaccination reduced child mortality by a third (other studies have produced much higher estimates), and only 4% of that reduction was due to vaccines preventing children from contracting measles. This is the mysterious power that Abi calls the “nonspecific effect” .”

Unexpected surprise

For more than a century, certain vaccines have been giving us hidden additional protections far beyond our expectations.

Evidence from trials in the poor African country of Guinea-Bissau suggests that vaccines tend to prevent other diseases.

These mysterious effects not only keep us safe through childhood but also reduce the risk of death at every stage of life. The Guinea-Bissau study found that people who were scarred by the smallpox vaccine were 80 percent more likely to be alive three years after the study began, while in Denmark, scientists found that among those vaccinated against tuberculosis in childhood,42 % are less likely to die of natural causes until they reach age 45. The same is true in dogs: An experiment in South Africa found that dogs who had been vaccinated against rabies had much higher survival rates, far exceeding expectations that they would be immune to rabies.

Other lucky surprises include keeping us away from pathogens completely unrelated to our target, reducing the severity of allergies, fighting certain cancers, and helping prevent Alzheimer’s. The TB vaccine is currently being tested for its ability to protect against the new coronavirus, even though the microbes behind the two diseases are completely different — one caused by bacteria and the other by viruses. There is an evolutionary process of 3.4 billion years between the two.

Despite decades of research, the secret sauce of these mysterious effects has not been revealed. But scientists were reluctant to make it work for me until we knew it, so this race was to find out what was going on.

Benefits of BCG

Abi’s work only confirmed the “non-specific effects” of vaccines in the 1980s, but scientists have long suspected that something strange happens when humans are vaccinated.

Take tuberculosis, one of humanity’s oldest enemies.

Humans have lived with this sausage-shaped bacterium for at least 40,000 years, and for most of human history, it felt like a death sentence. The bacteria, found in a third of ancient Egyptian mummies, may have been transmitted to Neanderthals. Since the beginning of the 20th century, the bacterium has claimed the lives of tens of millions of people, including visionary writer George Orwell, politician Eleanor Roosevelt, and bohemian Novelist Franz Kafka.

The turning point came when the French bacteriologists Albert Calmette and Camille Guerin invented the BCG vaccine. BCG is made by gradually changing the bacteria found in cattle, as many farm animals carry their own strains. First given to a child in 1921, by the 1950s it was clear that it was a game-changer; the vaccine was thought to be 70 to 80 percent effective at preventing the most serious diseases.

Early on, scientists noticed that BCG was associated with a dramatic drop in child deaths in the first few months of life. This is always troubling – unlikely because the vaccine prevents severe cases of tuberculosis, as the disease usually takes a while to develop. “It’s down by almost 70 percent,” said Mihai Netea, an immunologist at the University of Nijmegen in the Netherlands. “So from the outset, the beneficial effects were considerable.”

immune training

One possible explanation for some vaccines that protect us from microbes is that they share antigens—molecules that the immune system uses to recognize foreign invaders. For example, BCG may expose the body to a specific protein that is also present in another bacteria or virus. However, this particular vaccine also protects against other infections, so it seems unlikely that they have the same antigen.

Another view is that vaccines inadvertently provide the immune system with more general training. Recent studies have found evidence to support this idea, including a finding that a group of young adults who were treated with BCG and then exposed to pathogens other than tuberculosis developed different immune responses than unvaccinated people.

Surprisingly, this suggests that these strange beneficial effects do not come from the adaptive immune system—the kind that vaccines are designed to trigger, including cells that learn to seek out specific pathogens. These beneficial effects are the innate immune system. This is unusual because this more primitive, general defense system is not thought to have evolved and adapted in the same way.

“BCG reprograms the DNA of the immune system,” Abi said. “That means you’ve developed immunity against TB, but you’ve also trained the immune system.”

This may explain why vaccines also protect against certain cancers and dementia since the immune system plays an important role in the development of both. Our immune cells are constantly searching the body for mutated tissues to destroy, and cancer is significantly more common in people taking Meanwhile, lingering inflammation has long been linked to Alzheimer’s disease, which is linked to immune conditions such as Crohn’s disease.

Surprisingly, BCG is now the standard treatment for non-invasive bladder cancer, and one of the most successful treatments of its kind. Bladder cancer patients who have received the vaccine are less susceptible to Alzheimer’s, and a clinical trial is underway to see if it can reduce the incidence of plaque. Plaques are abnormal protein clumps associated with the disease.

Abi explained that while vaccination is good, these unexplained beneficial effects tend to be stronger with higher doses. “Somehow, the immune system responds positively to the boost,” he said.

Many of us are given the BCG vaccine in the first few months of life, which essentially boosts the human immune system.

BCG is thought to reprogram the DNA of the immune system.

In fact, it seems that it’s not just vaccines that do this. Those who are naturally infected with pathogens such as measles and survive have better long-term survival prospects than those who are never infected. The reason is unclear, but again, it is due to the immune training the body receives to help fight other diseases.

Curiously, while these potential benefits are already credited with saving millions of lives each year, Abiy believes their potential has not been maximized. “I would rather say the opposite,” he said. First, these factors are not currently considered when designing vaccination programs. This is problematic because not all vaccines have the same production capacity.

Vaccine effects are divided between men and women

The measles vaccine is an example. When Abiy and his team introduced a new vaccine to Guinea-Bissau in the 1990s, they were shocked to find that it doubled the mortality rate for girls but not boys. Years later, they realized why.

Various vaccines, including pertussis, polio, smallpox, yellow fever, and influenza, have nonspecific effects, but they work best among vaccines that contain live viruses. These “live” vaccines are made by using pathogens that are still capable of replicating themselves and weakening them to make them less harmful. “Inactivated vaccines,” on the other hand, involve bacteria or viruses that have been “killed” by heat or chemicals so that they cannot reproduce.

Live vaccines have hidden benefits that inactivated vaccines do not, so the order in which live vaccines are administered is important.

There is now growing evidence that if children are given live vaccines followed by inactivated vaccines, it negates some of the benefits it would have had.

Before the introduction of the new measles vaccine in Guinea-Bissau, the normal practice was to receive an inactivated diphtheria, pertussis, and tetanus (DTP) vaccine at 9 months followed by a live measles vaccine. But the new vaccine was given four months later, meaning DTP was the last to be given. (Other inactivated vaccines, such as polio, may also undermine beneficial effects if they are not administered in sequence.)

While scientists are now aware of the importance of the sequence of vaccinations, Abi said it is still not routinely considered, so many children may miss out on their hidden benefits.

It’s unclear why the sequence of the vaccine only affects girls, in part because there’s been so little research on how male and female immune systems differ. “Somehow, immunology is gender-blind,” Abiy said. “If you read research on mortality in low-income countries, there are no boys and girls, only children,” he said. “So we think mortality has to be the same for gender, but it’s definitely not. “

Although wild smallpox is being eradicated, treatment with a smallpox vaccine can provide other health benefits.

Studies have repeatedly shown that women have stronger immune systems than men—they are less likely to become seriously ill from infections, less likely to develop cancer, or have overreactions such as autoimmune diseases and allergies. Women also had a stronger immune response to vaccination.

“Women’s immune systems are very different, and for obvious reasons, they want to be able to conceive without rejecting the fetus. So you have to have an immune system, with more complex feedback mechanisms. It’s been like that from birth,” Abi said.

An estimated 1.1 million more deaths each year could be avoided if the unintended effects of vaccines and how best to benefit from them were taken into account when planning vaccination regimens. Likewise, ignoring their consequences can be disastrous.

Eradicating the paradox

In 1980, the World Health Assembly declared that after a long and tenacious campaign to vaccinate the world’s children against smallpox, smallpox had been eradicated. But when the virus was driven to extinction, something else disappeared too — vaccines. In the UK, children born after 1971 are not given the vaccine, which could have serious implications for their health.

“In Guinea-Bissau and Denmark, the smallpox vaccine had a very strong beneficial effect. But when we removed the vaccine, no separate studies were showing what that meant,” Abi said.

Afghanistan is one of the few regions where polio has not yet been eradicated.

Now, the world is on the verge of another victory. Polio has spread from almost every corner of the globe, and after Nigeria was eradicated, Africa was officially declared free of the virus earlier this month. The virus is now only found in small parts of Afghanistan and Pakistan.

This makes one worry about what will happen next. Like the smallpox vaccine, the polio vaccine is accompanied by a large number of nonspecific effects. For example, in 2004, although polio was almost completely eradicated in Guinea-Bissau, it somewhat reduced child mortality by about 67%.

“It could be that when we eradicated the disease, we stopped live vaccines. What we thought was a good thing was actually increasing mortality,” Abiy said.

The anti-vaccine movement has been falsely stoking skepticism about vaccines for decades, but ironically, the only secret they hide is that they do more for humans than anyone imagined.