Vaccines have been with us for more than 300 years and for the most part, have been rather successful at improving global health. However, some pathogens have been able to evade this approach. One of the most elusive enemies has been tuberculosis. This disease, caused by the bacterium Mycobacterium tuberculosis, has been plaguing us for millennia. Today, it infects millions per year and is considered one of the top ten causes of death worldwide.
Attempts to vaccinate humans against the bacterium date back to 1921, when researchers Albert Calmette and Camille Guérin, developed a candidate called not surprisingly, the Bacille Calmette-Guérin vaccine, shortened to BCG. This vaccine was based on a bovine cousin of the human pathogen, Mycobacterium bovis, and showed some significant promise in animals. It's not perfect but has stood the test of time. Today, the vaccine is used around the world as a means to reduce the risk for infection and progression of the disease
While BCG can help prevent infection, the vaccine may also have another benefit. Back in the 1990s, a Canadian group of researchers discovered an odd link between vaccination and a reduction in a completely different disease, Type 1 Diabetes. Although the vaccine could not prevent diabetes, for some reason, the onset of the disease appeared to happen later in life.
Attempts to explain this phenomenon led researchers to look at the immune system. It's involved both in responding to a vaccine and also for the troubling effects of Type 1 Diabetes. They figured there may be some type of overlap between the two. If they could identify what was happening at the molecular level, they might be able to identify a possible means to help treat the disease.
Eventually, a possible reason was found in 2012. An American team of researchers performed a clinical trial to determine if vaccination could act as a treatment for diabetes. The trial went quite well and suggested the mechanism of action happened to be suppression of the type of immune response that leads to autoimmunity. Interestingly, this had already been seen nearly 40 years earlier but no one seemed to take notice at the time.
While this explanation may have provided some help in explaining the strange result, it was not specific enough at the molecular level to determine whether BCG really could be valuable in helping those with Type 1 Diabetes. For that to happen, a more thorough examination would be needed.
Eventually, an answer was found although it seemed to be too good to be true.
Earlier this year, some of that same team from 2012 brought that mechanism to light. They published a study explaining how BCG affects us at the cellular level. The results help to explain both the reason for the delayed onset of diabetes as well as the why it may have value as a treatment.
The team recruited 282 people, of which 211 had diabetes and 71 didn't, acting as controls. These individuals had participated in an earlier BCG trial in which some had been vaccinated with BCG while others had been given a placebo. This provided the team with enough to be able to develop consistent results.
While the molecular mechanism was the goal, the trial itself focused on identifying whether or not BCG could help to reduce blood sugar levels, a key problem for those with diabetes. The participants were tested over the course of eight years to determine whether there were any changes in the concentration of blood glucose over that time.
When the results came back, the team was surprised to see that vaccination led to a reduction in blood sugar almost immediately. The levels in the first two years appeared to be about five per cent lower on average. But from the third year on, that drop was dramatic compared to the controls. While those who did not receive BCG saw slight increases in their blood sugar, those who got the vaccine saw their levels drop up to 18 per cent in the third year.
While this result was promising, it didn't provide an answer as to why this was happening. For that, the team had to look even deeper to determine what was happening. Eventually, an answer was found although it seemed to be too good to be true.
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The vaccine had improved the way our bodies use glucose.
The results revealed more glucose was being used leading to a reduction in the amount found in the blood. It was an incredible discovery in that it had nothing to do with diabetes, but all types of blood sugar problems. Although the best results would take a few years to achieve, the potential for its use appeared clear.
For the authors, this result opens up the door to more clinical trials and possibly treatment development, not just for diabetes but other types of health problems related to blood sugar levels. Granted, this will take many years to accomplish, but the end result may be well worth the wait. After all, BCG is a safe and already proven option with nearly a hundred years of history.
Finding a way to re-purpose it to help a completely different population may be an excellent way to improve our global health.
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