Dr. Tobias Kollmann and colleagues from around the world have identified what makes the TB vaccine so effective at preventing newborn deaths from diseases other than TB.

Bacillus Calmette-Guérin (BCG) is one of the oldest, safest and cheapest vaccines available and has been known to provide protection to newborns beyond its intended purpose of fighting off TB since at least the 1940s, but until now no one has been able to explain why.

In a new study, published in Science Translational Medicine, the researchers reveal how they identified a dramatic and rapid increase in neutrophils—white blood cells that patrol the body and destroy invading bacterial pathogens—in mice and babies within three days of BCG vaccination.

Tobias Kollman
Dr. Tobias Kollmann

The five-year study, conducted largely at BC Children's Hospital, is the first to demonstrate the beneficial mechanism triggered by administration of BCG in newborns. Involved in the study were  senior co-authors Dr. Tobias Kollmann, an affiliate investigator at BC Children's, and Dr. Nelly Amenyogbe, a former trainee at the BC Children's and graduate of UBC’s experimental medicine program. The study’s lead author is Byron Brook, a UBC PhD candidate in experimental medicine based at the Kollmann Lab at BC Children’s.

“It’s been known for a very long time that neutrophils play a very important role in managing sepsis, but until now nobody understood the role of BCG in initiating this critical process,” said Dr. Amenyogbe. “It was actually thought to be biologically implausible, however we’ve not only shown how BCG is involved, but that it kicks off this process almost instantly following vaccination — far more quickly than anticipated.”

The researchers first witnessed the phenomenon—known as emergency granulopoiesis (EG)—in mice, with the team later validating it in blood samples from newborn babies in West Africa and Papua New Guinea.

Dr. Nelly Amenyogbe
Dr. Nelly Amenyogbe

Kollmann, who is also the head of the Systems Vaccinology team at Telethon Kids Institute (TKI) in Australia in partnership with the Perth Children’s Hospital Foundation, said the findings reinforce how critical it is for newborns in low-resource settings to receive BCG immediately after birth. Kollmann was previously the head of the paediatric division of infectious diseases at UBC before relocating to Australia.

“Less than half the babies who should get this vaccine right after birth actually get it then, partly because of logistics and partly because TB is not seen as a huge risk in those first few weeks. Administration is often delayed to four to six weeks, but by then it’s too late for many newborns,” said Kollmann, also an affiliate professor in the UBC department of paediatrics. “Around half of all newborn deaths from infection happen in the first week of life, with about 75 per cent of those deaths caused by sepsis. Given BCG’s clear role in helping newborns to fight off sepsis, we could save the lives of close to a million newborns every year if they were given this vaccine within days of birth instead of weeks later.”

Brook, the study’s lead author, said,

“If every newborn was vaccinated with BCG, the greatest impact would be in regions of highest newborn mortality, specifically low- and middle-income countries. It could also help save newborns here in Canada, and represents a new strategy of how to get more benefit from existing vaccines.”

Byron Brook
Byron Brook

The researchers cautioned that while the effect was rapid and offered robust protection against newborn sepsis, it was relatively short-lived and did not occur in adult mice.

Dr. Kollmann and Dr. Amenyogbe are also involved in Australia’s BRACE trial, which is testing BCG’s potential to fight off COVID-19. Kollmann said whether BCG may or may not be protective against COVID-19 remains to be seen, but in the meantime, its real and proven potential to save the lives of vulnerable newborns had to be maximised.

“BCG is very, very safe, costs only a few cents per dose, and reduces infectious causes of mortality—not just tuberculosis—in newborns by almost 50 per cent,” said Dr. Kollmann. “There’s nothing that we have in our entire current medical arsenal that is as effective, cheap, safe, feasible and affordable as this vaccine. All we have to do is ensure all newborns at risk get it right away at birth.”

Credit: UBC News Story May 6, 2020