The TB vaccine mysteriously protects against many things. Now we know why

An amazing story happened when babies in the African countries of Guinea-Bissau and Uganda were given the TB vaccine.

Instead of a vaccine against targeted bacteria – Mycobacterium tuberculosis – the tuberculosis vaccine offered broad protection against a range of unrelated infections, including respiratory infections and serious complications such as sepsis.

Australian researchers have now identified the biological mechanism behind the off-target effects of the TB vaccine.

The team administered the Bacille Calmette-Guérin (BCG) vaccine to 63 infants within ten days of birth and compared their progress with a control group of 67 infants who did not receive the BCG vaccine.

The researchers took blood samples from the infants and examined white blood cells, called monocytes, in both groups.

Monocytes are part of the human body’s innate immune system, which provides the first line of defense against pathogens and are not specific to any disease.

Looking at these monocytes, the researchers found clear epigenetic differences between the vaccinated and unvaccinated group that lasted an average of 14 months after vaccination, changing the way genes are expressed, or controlling which genes are active and which are turned off.

In vaccinated infants, the BCG vaccine generally reprogrammed or “trained” monocytes to be more responsive to pathogens, and this epigenetic mark was passed on to the next generation of monocytes for more than a year after vaccination.

Researchers say this is the mechanism behind the broad, protective effect of BCG vaccines seen in African countries.

“We have shown for the first time how the BCG vaccine can have long-lasting effects on the immune system of infants,” says Boris Novakovic, senior author and molecular biologist at the Murdoch Children’s Research Institute (MCRI) in Melbourne, Australia.

Researchers have also used in vitro Experiment to study these epigenetic changes in detail.

They isolated monocytes from healthy adults, exposed the cells to two types of BCG vaccine, and found distinct changes in different types of epigenetic modifications.

These include DNA methylation—molecular tags that favor DNA sequences—and histones—bulky proteins that surround DNA strands.

Monocytes respond to stimuli through receptors on the cell’s outer surface.

When these receptors bind to a pathogen, they trigger the monocyte to “eat” the pathogen (phagocytosis), which triggers a cascade of events within the cell where one protein is transferred to another and other processes are altered. cell gene expression.

Exposure to the BCG vaccine speeds up this process and repackages the monocyte DNA so that it can carry the genes required to respond to threats, Novakovic told ScienceAlert.

Stimulating monocytes makes them more responsive to all infections, not just tuberculosis.

It was previously thought that the innate immune system, unlike the adaptive immune system (which uses T cells and specific antibodies to remember previously encountered pathogens), cannot remember past infections.

In the past decade, scientists have discovered that the innate immune system can create a non-specific memory called “learned immunity.”

“It was a breakthrough,” Novakovic told ScienceAlert.

It’s not just the BCG vaccine that overreacts the innate immune system. Other live attenuated vaccines, which use a weakened form of the virus to protect against diseases such as polio, measles, and smallpox, have similar effects.

Conditions that cause stress to the body, such as obesity and high cholesterol or trauma, also make the innate immune system more responsive. This is not always a good thing.

Although the research by Novakovic and his colleagues focuses on the basic biological mechanisms of learned immunity, there are some real implications.

In countries with high infant mortality rates, vaccination against tuberculosis, measles, or smallpox has a beneficial effect on protecting infants against a number of other infections.

In the Australian context, where babies rarely die from infectious diseases, there is more interest in using the BCG vaccine to prevent allergies and eczema in children, Novakovic said.

It is thought that the BCG vaccine may have a beneficial effect on the developing immune system.

A study by MCRI researchers has been published Allergy Last year, BCG vaccination was found to have a small beneficial effect in preventing eczema in infants prone to developing the common skin condition.

Epigenetics research published Science Advances

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