Trials are underway to see if a vaccine that partially protects against a variety of diseases can add Covid-19 to the list, but the mechanism by which it provides such broad protection has remained mysterious. Now, one team may have a piece of the answer, with the potential to save a lot of lives.
The BCG vaccine is one of the world's oldest, dating back a century. It was designed to fight tuberculosis, still among the world's biggest killers, but it is only partially successful against tuberculosis. Not only that but the observation that BCG-vaccinated infants have an increased chance of surviving childhood can't be explained by tuberculosis prevention alone.
This has inspired a string of studies to conclude that BCG reduces death rates from an astonishing variety of bacteria, viruses, and even cancers – never offering 100 percent protection, but collectively saving millions of lives. Evidence is even emerging that BCG may reduce the severity of autoimmune diseases like Type 1 diabetes and multiple sclerosis.
Dr Nelly Amenyogbe and Professor Tobias Kollmann of the Telethon Kids Institute became interested in the demonstrated capacity of BCG to protect newborn children against sepsis, a major killer in some parts of the world. Studies in several countries have shown BCG administration shortly after birth can halve sepsis deaths. However, how BCG provides this protection was a puzzle. Vaccines take days or sometimes months to produce their immune effects, raising the question of how BCG could work against something that takes hold so quickly after birth.
In Science Translational Medicine, Amenyogbe and Kollmann report that BCG vaccines given to mice produce an exceptionally swift increase in neutrophils, a type of white blood cell. They then found the same thing in children given BCG at birth in three countries.
Amenyogbe told IFLScience the “emergency neutrophils” are probably not the primary reason BCG works against other diseases. However, she sees no contradiction with previous work showing monocytes, a different type of white blood cell, are an important factor.
“BCG is fascinating because it potentially has so many different effects on different parts of the immune system and we are only just teasing these apart,” she said. Sepsis is unique because the speed of the response is so much more important than its longevity.
Benefits against lower respiratory tract infections reported in preliminary trials are likely achieved via other routes. These have inspired at least two trials of whether BCG vaccination can prevent frontline health care workers from catching Covid-19 from their patients. The results of these won't be available for months, and at a press conference Kollman stressed: “Nobody on the planet right now knows if BCG does anything beneficial for Covid-19. There is no evidence right now, that is why we are studying it.”
That's not the case for many other conditions, and Amenyogbe is passionate about getting BCG into more widespread use, particularly in countries with high infant mortality. BCG, despite being one of the cheapest vaccines around, is often not given in countries where tuberculosis is rare due to its perceived reputation as a tuberculosis-fighter. Moreover, since it comes in 20-dose vials, doctors often don't give BCG to children at birth and wait until they can vaccinate a group, making it too late to fight neonatal sepsis.
Amenyogbe doesn't expect her work on BCG's mechanisms to lead to an improved version in the near future, instead hoping the explanation will encourage more widespread and earlier application.
Although BCG is the vaccine most studied for providing protection against diseases besides it original target, it's not the only one. “There is an entire field known as the non-specific effects of vaccines,” Amenyogbe said.