New research suggests that the Bacillus Calmette-Guérin (BCG) vaccine—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.
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.
For this study, published in Communications Medicine, researchers conducted two related one-year, open-label clinical trials of BCG immunotherapy in 23 adults aged 55 years and older. The cohort included 11 adults with Alzheimer’s pathology and 12 adults without. Cerebrospinal fluid (CSF) and peripheral blood samples were obtained from participants at regular intervals after vaccination.
The results showed that BCG promoted enhanced immune responses to other immune challenges, suggesting broader effects on immune function. Notably, the heightened immune responsiveness was not accompanied by an increase in inflammatory markers, which is a known risk factor for neurodegeneration.
BCG also shifted the levels of amyloid-beta—a key biomarker of Alzheimer’s disease—in the CSF and bloodstream. In healthier participants without Alzheimer's disease pathology, amyloid levels declined significantly in brain and spinal fluid, while increasing in blood samples over 12 months. This shift in balance was not observed in participants with Alzheimer’s pathology, indicating no measurable effect in this group, and suggesting that the timing of administering BCG might affect early disease dynamics and protein clearance from the central nervous system.
Of critical note is that the study tested a specific vaccination strategy in older adults, not including BCG vaccination in childhood, which is common in many countries.
The authors note that further research, including placebo-controlled studies, is needed to investigate the relationship between BCG and Alzheimer’s disease.
Data from Mass General Brigham