100-Year-Old Tuberculosis Vaccine Boosts Babies’ Frontline Immune Defense

Australian researchers have found that the widely used tuberculosis vaccine also protects against many unrelated infections and boosts immunity to protect newborns for more than a year.

The Bacillus Calmette-Guérin (BCG) vaccine for tuberculosis changes the way frontline immune cells create long-lasting biological ‘marks’ in their DNA, reading genetic instructions to fight off the virus. researchers said.

“DNA is like a manual for the cell. It tells us what it can and cannot do,” study author Boris Novakovich, a molecular immunologist at the University of Melbourne, told VOA. “You might have a sentence that says ‘if you find the virus, turn on the next gene’. What we did with the BCG vaccine [is] a kind of [change] Make the period at the end of the sentence an exclamation point. ”

The survey results are scientific progress journal.

“What is new here is the durability and long-lasting imprinting effect of the BCG vaccine at birth in Australian babies. [that] they can show [in detail] How that happens,” vaccine epidemiologist Christine Stabell Benn of the University of Southern Denmark said in an interview with VOA. She was not involved in the study.

Developed over a century ago, the BCG vaccine contains weakened live bacteria. It is one of the oldest vaccines still in use and the most frequently administered vaccine in the world.

Decades ago, Ben and her colleagues found that Guinea-Bissau children vaccinated against tuberculosis were less likely to die from other unrelated diseases. Confirming this, they show that low-birth-weight infants who receive BCG at birth are about one-third less likely to die in the first month of life than those who receive BCG later on a regular schedule. Subsequent trials in Guinea-Bissau and Uganda supported these findings.

Today, this “non-specific effect” of BCG vaccination has been observed in babies, healthy adults, and the elderly. Clinical trials are underway to see if it helps protect against COVID-19.

There is growing evidence that BCG trains the innate immune system.

However, it was only recently that scientists began to understand how this “trained immunity” that the BCG vaccine produces actually works.

Previous studies have seen traces of trained immunity one to three months after BCG vaccination in adults. But vaccines are usually administered to young babies, and scientists hadn’t tested whether the training would last long.

Novakovic and his colleagues compared the immune cells of 63 newborns who received the BCG vaccine soon after birth with those of 67 unvaccinated newborns. They found that exposure to BCG leaves a mark on virus-fighting regions of the genome, instructing cells to activate specific genes to a greater or lesser extent. We’ve passed these marks from generation to generation as we make them. Traces of trained immunity persisted for more than 1 year.

Laboratory tests using cultured human immune cells have allowed scientists to piece together the cellular machinery involved in making these marks with greater precision than before.

“We were able to look at all these different levels and see in a very comprehensive way what happens when these cells are directly exposed to BCG.

Novakovic, who also works at the Murdoch Institute for Pediatrics, said future studies would like to see if the findings apply to different populations, particularly where infectious diseases are more common than in Australia. And long-term, he believes, scientists should design vaccines that specifically target immune-enhancing pathways that BCG accidentally activates.

“The BCG vaccine is great. It’s safe and it works. rice field. “Imagine being able to create a purely trained immune vaccine.”

Benn said future studies should take into account factors such as gender and maternal vaccination status, which epidemiologists have found may influence immune boosting with BCG. , she said, during the first few weeks of life, boys seem to benefit more from the vaccine’s additional protection than girls.

But beyond further research, Ben hopes the new research will give public health officials confidence in off-target immunity from BCG. BCG should be recommended not only as a tuberculosis vaccine, but as a protection against death from infectious disease, she says.

“We feel like we’re sitting on our hands,” she says, “waiting for biological mechanisms while the children are saved.