How the tuberculosis vaccine spikes the immune system to protect the body from other diseases

The vaccine induces epigenetic changes and “trains” our innate immune system.

The Bacillus Calmette-Guerin (BCG) vaccine is the most widely used vaccine in the world, approximately 100 million newborn children worldwide receive it annually. Mostly used to protect against tuberculosis, it also reduces child mortality rates, mainly by reducing lower respiratory infections. The vaccine is even used as a treatment against bladder cancer. Up until now, however, researchers were in the dark about how the tuberculosis vaccine impacted the immune system and protected against these other diseases on a cellular level.

In a new study, Mihai Netea from the Radboud University Medical Center in the Netherlands and his team show how the vaccine induces metabolic and epigenetic changes in monocytes, certain white blood cells that are part of our innate immune system. These changes affect gene activity without changing the gene’s DNA sequence. The researchers call the process “trained immunity.” This trained immunity allows the cells to be more responsive against pathogens they reencounter. “Immune genes are easier transcribed after BCG vaccines in cells of innate immunity,” says Netea.

Our innate immune system is our first line of defense against invading pathogens: it is very rapid and non-specific. Up until recently, researchers thought that the cells of the innate immune system don’t “remember” pathogens they’ve previously encountered. It was thought that the cells of our adaptive immune system, like T and B lymphocytes, could recognize pathogens they already knew, but that macrophages, monocytes and natural killer cells lacked this capacity. "These findings change the concept that the innate immune system cannot adapt in the long-term after an infection or vaccination," Netea says. However, he says that early indications show that there is significant variation in trained immunity from one individual to the next.

Netea’s discovery may also apply to other vaccines: “Epidemiological studies suggest that other vaccines with live microorganisms such as measles, oral polio vaccine or variola vaccine have similar non-specific protective effects.”

Netea sees several opportunities for drug development in his findings: “There’s the possibility to combine classical immune memory with trained immunity, to improve the effectiveness of vaccines. You could boost the response to classical vaccines in individuals at risk by activating trained immunity. You could also restore immune responsiveness in patients with weak immune systems.”

Feature image: CDC/Dr. George P. Kubica on Wikimedia