The TB Vaccine Mysteriously Protects Against Many Things. Now we know why

Something remarkable happened when babies in Guinea-bissau and Uganda were given the tuberculosis vaccine.

The tuberculosis vaccine provided broad protection against a variety of unrelated infections, including respiratory illnesses and serious complications such as assepsis.

The biological mechanism behind the off-target effects of the tuberculosis vaccination has been pinpointed by Australian researchers.

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

Researchers took blood samples from infants and examined circulating white blood cells called monocytes in both groups.

Monocytes are a component of the human body’s innate immune system, which is the first line of defense against pathogens and isn’t specific to any particular illness.

Researchers found distinct epigenetic differences between the vaccinated and the non-vaccinated group, which lasted for average 14 months after vaccination.

The BCG vaccine reprogrammed or ‘trained’ monocytes to be more adaptive to pathogens in general, and this epigenetic signature was passed down to the next generation of monocytes for more than a year after immunization.

According to the researchers, this is the mechanism that leads to a widespread, protective effect of BCG vaccinations in African nations.

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

The researchers also conducted an in vitro study to investigate these epigenetic changes in depth.

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

DNA methylation molecular tags adorn the DNA sequence, andhistones are large proteins around which DNA strands are wound.

Monocytes respond to pathogens via receptors on the cell’s outside surface.

When these receptors contact a pathogen, it triggers the monocyte cell to ‘eat’ the pathogen (phagocytosis), which also triggers a cascade of events inside the cell, where one protein switches on another protein, and so on, until this triggers a mutation in the cell’s gene expression.

Novakovic told ScienceAlert that prior exposure to the BCG vaccine repackages the monocyte DNA in a way that accelerates the whole process and gets the genes required to respond to threats on time.

Monocytes are more adapted to all infections, not just tuberculosis, by putting them on high alert.

In the past, it was assumed that the innate immune system had no way of remembering previous infections, unlike the adaptive immune system (which uses T cells and specific antibodies to remember pathogens it has encountered previously).

Scientists have discovered that the innate immune system can actually create a non-specific memory, called ‘trained immunity,’ over the last decade.

“That’s been the breakthrough,” Novakovic told ScienceAlert.

The innate immune system is hyperresponsive to not only the BCG vaccine, but other live attenuated vaccinations that protect against diseases such as polio, measles, and smallpox also have a similar effect.

Conditions that put stress on the body, such as obesity, high cholesterol, or injuries, also increase the immune system’s responsiveness. That’s not always a good thing.

Although Novakovic and colleagues’ research focused on the biological mechanisms of trained immunity, there are still some issues that may arise in the real world.

Vaccinating against tuberculosis, measles, and smallpox may be beneficial in preserving infants against a range of other infections in countries where infant mortality is high.

According to Novakovic, there is increasing interest in the use of the BCG vaccination to prevent allergies and eczema in children in an Australian context where babies rarely die of infectious diseases.

The assumption is that the BCG vaccine might have a beneficial effect on the developing immune system.

BCG immunization had a modest beneficial effect in preventing eczema in infants predisposed to developing the common skin condition, according to a research published last year in Allergy.

The epigenetics research was published in Science Advances.

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