Tuesday, November 29, 2022

Century-old TB vaccine boosts infants’ front-line immune defense

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Researchers in Australia have found that the widely used tuberculosis vaccine also prevents several unrelated infectious diseases, and that its immune boost can protect newborns for more than a year.

Researchers say the Bacillus Calmette-Guérin (BCG) vaccine for tuberculosis causes front-line immune cells to form long-lasting biological “marks” on their DNA, allowing them to carry out genetic instructions to fight the virus. read.

“DNA is like the manual for the cell. It tells you what it can and can’t do,” study author and molecular immunologist Boris Novakovic of the University of Melbourne told VOA. “You can have a sentence that says, ‘If you see a virus, turn on the following gene.’ And what have we done with the BCG vaccine? [is] like [change] Full stop for the exclamation mark at the end of that sentence.”

The findings were published in science advance magazine.

“What’s new here is the durability, the long-lasting effects of the BCG vaccine at birth in these Australian babies, and also [that] they can show [in detail] How does it happen,” said vaccine epidemiologist Christine Stabel Benn of the University of Southern Denmark in an interview with VOA. She was not involved in the study.

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

Decades ago, Ben and his colleagues observed that children in Guinea-Bissau who had received a tuberculosis shot were less likely to die from other, unrelated diseases. They later confirmed this in a randomized trial, which showed that low birth weight babies who received BCG at birth were about a third less likely to die in the first month of life than those who received BCG at normal times. . Subsequent trials in Guinea-Bissau and Uganda confirmed these findings.

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Today, this “non-specific effect” of BCG vaccination has been observed in infants, healthy adults and the elderly. The immune enhancement of the vaccine is used to treat bladder cancer. Clinical trials are underway to see if it can help protect against COVID-19.

There is increasing evidence that BCG trains the innate immune system – a non-specific, rapid-acting response that is activated to fight off a wide range of threats.

But it wasn’t until recently that scientists began to figure out how the BCG vaccine that produces “trained immunity” actually worked.

Previous studies found traces of trained immunity one month to three months after BCG vaccination in adults. But the vaccine is usually given to young children, and scientists hadn’t tested whether the training could last long.

Novakovic and his colleagues compared the immune cells of 63 newborns who received the BCG vaccine right after birth with those of 67 babies who had not received the vaccine. They found that exposure to BCG marks the virus-fighting regions of the genome that tell cells to activate specific genes more or less frequently. Immune cells pass these marks on from generation to generation as they divide to make new cells. Traces of trained immunity remained for more than a year.

In laboratory tests using cultured human immune cells, scientists were able to piece together the cellular machinery involved in making these marks more precise than previously thought.

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“We were able to look at all these different levels, in a really comprehensive way, of what happens to these cells when they are directly exposed to BCG,” Novakovic said.

In the future, Novakovic – who also works at the Murdoch Children’s Research Institute – said he would like to see if the study’s findings hold up in different populations – especially in places where infectious disease is more common than in Australia. . And in the long term, he believes, scientists should design vaccines that specifically target the immune-enhancing pathways that are activated by concomitantly with BCG.

“The BCG vaccine is great – it’s safe, and it works. But it’s a little dirty way because we don’t really know what it does. We just know that it works,” he said. “Imagine you could make a fully trained-immune vaccine.”

Ben said future studies should consider factors such as sex and immunization status of the mother, which epidemiologists have observed can boost immunity from BCG. For example, boys benefit more from the added protection of the vaccine than girls during the first weeks of life, she said.

But beyond more research, Benn hopes the new study will give public health officials more confidence in off-target immunity from BCG, a vaccine she says should be recommended as a protection against death from infectious disease. Not just as a tuberculosis vaccine.

“I feel like we’re sitting on our hands,” she said, “waiting for the biological system while the children can be saved.”

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