Understanding How The TB Vaccine Protects Against Other Diseases

Scientists may be closer to understanding how the tuberculosis vaccine may help protect the body against diseases other than just tuberculosis.

In a recent study published online in Cell Reports, a team of researchers described how this non-specific protection occurs because of “trained immunity.” The Bacillus Calmette-Guerin (BCG) vaccine induces metabolic and epigenetic changes in white blood cells that influence gene activity without affecting the gene’s DNA sequence.

“BCG-induced trained immunity results in an increased responsiveness of monocytes and macrophages, with effector functions such as cytokine production and reactive oxygen species release being increased upon secondary stimulation with non-related pathogens,” wrote Rob J. W. Arts, from Radboud University Medical Center, Nijmegen, the Netherlands, and colleagues.

According to the authors, the BCG vaccine is the most commonly used vaccine worldwide. In addition to the protection it offers against tuberculosis, they also highlight its ability to protect against other conditions, including lower respiratory tract infections in children, asthma, and even bladder cancer.

They also added that the non-specific protective effects of BCG vaccine are thought to be a result of “trained immunity”—a process involving long-term metabolic changes and chromatin remodeling through modification of histones in white blood cells, such as monocytes, in the innate immune system; histones are scaffold proteins that DNA wraps itself around in the nucleus. Trained immunity enables immune cells, such as monocytes, to better recognize and mount more effective responses against known pathogens.

However, data to explain exactly how the BCG vaccine offers this wide-ranging protection have been lacking. With this in mind, Arts and colleagues performed a study to investigate the metabolic pathways that might underlie this effect.

They conducted in vitro and in vivo (in mice and in humans) studies to examine metabolic changes that occurred in monocytes after BCG vaccination. They found that a shift in cellular glucose metabolism, in favor of glycolysis, was needed to set off trained immunity.

The researchers showed that BCG vaccination resulted in a strong increase in glycolysis in both mice and humans, with a less pronounced increase in glutamine metabolism; these vaccine-induced metabolic changes were needed to result in histone modifications. They also found that induction of glycolysis is critical to stimulate trained immunity after BCG vaccination in human volunteers. According to the authors, genetic variation of key enzymes involved in glycolysis also impaired the induction of trained immunity in monocytes in human volunteers.

Overall, these findings show that a change in cellular metabolism is crucial for BCG-induced trained immunity. In particular, a shift in glucose metabolism toward glycolysis is necessary to trigger the histone modifications and functional changes that are central to BCG-induced trained immunity.

“Deciphering the role of metabolic pathways for the non-specific effects of BCG vaccination may lead to a better understanding of the induction of trained immunity and how modulation of cellular metabolism pathways may be used to boost the effect of vaccines,” the authors concluded.

Dr. Parry graduated from the University of Liverpool, England in 1997 and is a board-certified veterinary pathologist. After 13 years working in academia, she founded Midwest Veterinary Pathology, LLC where she now works as a private consultant. She is passionate about veterinary education and serves on the Indiana Veterinary Medical Association’s Continuing Education Committee. She regularly writes continuing education articles for veterinary organizations and journals, and has also served on the American College of Veterinary Pathologists’ Examination Committee and Education Committee.