Scientists are looking for a new and improved vaccine to prevent tuberculosis (TB). Fortunately, a new approach might enable them to use an existing vaccine, just with a few modifications. From the University of Montreal, scientists are developing an updated TB vaccine.
TB is caused by a bacterial species called Mycobacterium tuberculosis (Mtb), which is uniquely capable of living and growing inside immune cells called macrophages that are supposed to kill the bacteria. The BCG (bacille Calmette-Guerin) vaccine was introduced in 1921 but has since been largely ineffective at preventing TB infections. Some antibiotic treatments are available to treat the disease, but their value is questioned given their contribution to antibiotic-resistant TB strains and potential toxicity.
“We are in serious trouble with this bug if we don't investigate an alternative approach," said lead corresponding author Dr. Maziar Divangahi.
The new approach from scientists at the University of Montreal involves boosting the innate immune response to TB by reprogramming immune stem cells with the BCG vaccine. The innate immune system is the non-specific, first-responding wing of the immune system. By giving the BCG access to the bone marrow, researchers found that they could activate innate immune system macrophages to better engulf and kill TB.
Despite making the connection between the BCG vaccine, the bone marrow, and macrophage activity, Divangahi and others were still unsure of what was happening on a molecular level to change the immune response to TB.
"Although we demonstrated that BCG educates stem cells to generate trained immunity, we had no idea about the molecular mechanisms that were involved in this protective pathway,” Divangahi explained.
They investigated further to elucidate the genomic pathways connected to BCG, stem cells, and trained immunity and found that BCG access to the bone marrow changes the “transcriptional landscape” of immune stem cells. These changes were responsible for giving macrophages the power to kill TB as opposed to falling victim to the bacteria growing inside of them.
Going forward, scientists still have a lot to learn about the effect of giving the BCG vaccine access to the bone marrow, but the present study’s results indicate a new beginning, a new look at an old vaccine.
The present study was published in the journal Cell.