One vaccination against TB, diabetes, and MS?

Science News reports on the BCG vaccine, short for Bacillus Calmette-Guérin. Originally, it was a treatment to prevent tuberculosis, but now it’s showing promise for helping fight type 1 diabetes, Alzheimer’s disease, eczema, asthma, multiple sclerosis, and, of course, COVID-19:

Almost as soon as BCG was introduced in the 1920s, researchers noticed a drop in infant deaths in some places where the vaccine was used. Later studies revealed that the vaccine protects against a range of infections. Much more recently, a single dose of the vaccine reduced the risk of respiratory infections in elderly study participants compared with those who got a placebo, according to an October 15 report in Cell.

The vaccine appears to boost immunity in some situations, but paradoxically, BCG may also calm an overactive immune system.

“Everybody kept getting signals, often from human data, saying this microorganism is doing beneficial things … whether it was allergy or autoimmunity or multiple sclerosis or diabetes,” says immunologist Denise Faustman of Harvard Medical School. “Over the last 10 years, that dataset has just grown and grown.”

Faustman is in the midst of a 150-person safety and efficacy trial of BCG in adults with type 1 diabetes. Her team previously showed, in a small study published in 2018, that the vaccine can safely improve blood glucose control in patients with long-term disease who continued taking insulin. The vaccine appears to reprogram immune cells to take up extra glucose, her team reported in iScience in May 2020.

In the late 1990s and early 2000s, Faustman’s team and others found that a molecule called TNF alpha, which is made by some immune cells, could selectively kill the T cells that attack beta cells. Among its many jobs, TNF alpha fights bacterial infections and helps the body make T regulatory cells, or T-regs, which act as referees to prevent collateral damage during immune responses. For reasons that are not well understood, in people with type 1 diabetes, T-regs are either too few or defective. Faustman and others found that TNF alpha boosted T-reg numbers and activity in mice and in human cells.

But giving TNF alpha directly wasn’t an option; it was expensive and hard to administer safely. So Faustman’s team searched for something that could trigger immune cells to make TNF alpha on their own. “The answer that kept popping up was BCG,” Faustman says.

Another research group led by immunologist Bhagirath Singh, then at the University of Alberta in Edmonton, Canada, had found in the 1990s that BCG and a related immune stimulant called complete Freund’s adjuvant, or CFA, could prevent type 1 diabetes in mice prone to the disease. CFA, which is made with dead M. tuberculosis, also protected pancreatic cell transplants in diabetic mice from destruction by the immune system.

One of those researchers is Mihai Netea, an immunologist at the Radboud University in the Netherlands. He and his colleagues have shown that BCG triggers trained immunity, a nonspecific sort of memory that readies immune cells to react more strongly to any pathogen later on. It’s thought that this is how, in human studies, it protects against bacterial and viral infections, and is what’s led several research groups to test it as a prevention against COVID-19.

Netea’s team also reported in 2016 in Cell Reports that one shot of BCG triggers healthy volunteers’ monocytes to break down glucose at a higher rate, and increases the activity of genes required for glucose metabolism within the cells. Netea says he isn’t sure that these changes in immune cells are enough to affect glucose levels throughout the whole body, as Faustman posits.

In its ongoing trial, Faustman’s team is using radioactive glucose PET scanning to map out where the glucose goes after BCG vaccination. So far, they’ve seen increased glucose uptake in some of the places where monocytes and other immune cells are found, such as the spleen, bone marrow and descending aorta.

There’s a lot more at the link. You can read the Cell respiratory research here, Faustman’s diabetes research here, and Netea’s research here.