Many of us carry a small round scar on an upper arm to show we were vaccinated against tuberculosis when we were young. The BCG (Bacillus Calmette-Guérin) is the oldest vaccine still in continuous use. For more than 100 years it has been protecting children from this potentially fatal contagious disease.
Today, after a period of decline, tuberculosis cases are on the rise and it is now the deadliest infectious disease globally, surpassing Covid-19. While new vaccines are in development, the BCG remains the only one available.
Demand for the vaccine is further boosted by researchers exploring how it might be useful as a tool for training the immune system to prevent other conditions. It’s already in use as a treatment for bladder cancer and has been shown to be protective against the influenza A virus. One trial even found that it can protect against long Covid if administered during the Covid-19 convalescence period.
“It is very good at engaging with the immune system and is able to trigger these strong responses,” says cellular immunologist Kerry Hilligan from Wellington’s Malaghan Institute of Medical Research. “What was observed way back in the 1930s was that, in areas where the BCG vaccine was introduced, the children weren’t only protected against tuberculosis. They started seeing lower rates of all sorts of respiratory and viral infections.”
While modern vaccines are highly targeted ‒ teaching the immune system to recognise a specific threat ‒ the BCG is broader spectrum. A live attenuated vaccine, it contains a weakened form of the tuberculosis bug. “That means it’s got lots of different ways of interacting with the immune system,” says Hilligan. “We think these multiple conversations are important. Also, because it’s alive, the body doesn’t see it and immediately clear it. It can hang around for a little while. So the immune system doesn’t get this huge sugar-rush type of effect, but more of a slow training.”
Studies have shown that the BCG leaves us better prepared to fight off a variety of pathogens because it activates both the innate immune system, which is the body’s first line of defence, and the adaptive immune system, which is our immunological memory.
Hilligan believes there are lessons to be learnt from the way the BCG activates multiple arms of the immune system, and that fine-tuning these responses could lead to new treatments for cancer and infectious diseases, as well as more effective vaccines for tuberculosis.
In New Zealand the BCG is mainly given to high-risk babies. It is available to children under 5 who are either living with someone with tuberculosis or has a history of the disease, or because they or someone close to them may be exposed from time spent in a country with high rates of the disease. Being vaccinated doesn’t prevent infection entirely but helps stop serious illness.
While based at the National Institute of Allergy and Infectious Diseases in the US, Hilligan was involved in research that showed giving the BCG intravenously rather than injecting it just below the skin, as is the current practice, results in a strong immune response in the lungs.
Studies with animals showed that if the vaccine is delivered straight into the bloodstream it stops tuberculosis bacteria completely. “When the BCG enters the bloodstream it travels to important immune organs and helps reprogramme stem cells to produce more responsive immune cells,” explains Hilligan.
Now based at Malaghan, Hilligan is using the knowledge learnt about the BCG to look into how other common bugs might interact with our bodies.“We’re exposed to microbes all the time and these exposures are really important for educating our immune system to respond properly,” she says. “So we’re trying to build up a picture of how different microbial exposures leave their imprint on the immune system and see what we can learn from these beneficial interactions to develop more holistic therapeutics.”
Hilligan is particularly interested in aspergillus, a common fungus that lives in soil, and is tracking changes in the lungs of mice that inhale it then watching to see if they are protected against flu.
But she isn’t finished with investigating the potential of the BCG vaccine, either.
“I’m hoping to explore it further because I think there’s a lot more we can learn from the way it interacts with the immune system.”
