BCG vaccine may remodel the human brain's immune environment

New research led by Mass General Brigham investigators suggests that the Bacillus Calmette-Guérin (BCG) vaccine - which is delivered through the skin to prevent tuberculosis - may remodel the human brain's immune environment, offering a potential biological explanation for previously observed associations between BCG vaccination and lower Alzheimer's disease risk. The year-long study found that BCG promoted increased responsiveness in immune cells surrounding the brain and modified Alzheimer's-related biomarkers in older adults without evidence of Alzheimer's pathology, but not in those with biomarker evidence of the disease. Findings are published in Communications Medicine.

The immune system and the brain may be far more connected than we once thought. The next step is to test this rigorously in larger, controlled studies, particularly in prevention, where the hope would be to preserve brain health before significant Alzheimer's disease develops."

Steven Arnold, MD, senior and co-corresponding author, managing director of the Interdisciplinary Brain Center, Mass General Brigham Neuroscience Institute

Over the last two decades, researchers at Mass General Brigham have been studying multiple "off-target" benefits of the BCG vaccine in autoimmunity and infection, including ongoing Phase III clinical trials in type 1 diabetes and past Phase II and Phase III trials in COVID-19. Prior research involving preclinical models, retrospective studies, and randomized clinical trials has suggested that BCG can also reduce Alzheimer's risk and bring about trained immunity, boosting defenses against unrelated infections and correcting blood sugars. Most prior research on trained immunity has focused on blood, leaving unclear whether BCG influences immune cells in the fluid surrounding the brain and spinal cord as well.