an explorative study

In collaboration with dr. B. Cirovic and dr. A. Schlitzer, LIMES institute Bonn.

The Bacillus Calmette-Guerin (BCG) vaccine not only protects against Mycobacterium tuberculosis, but has also been shown to reduce morbidity and mortality caused by non-related infections. This effect is likely due to non-specific long-lasting immune modulatory effects. The effects of BCG vaccination on the innate immune system last longer than can be expected from the lifespan of peripheral blood mononuclear cells (PBMCs).  During the process of hematopoiesis, hematopoietic stem and progenitor cells (HSPCs) give rise to mature leukocytes of different lineages, including PBMCs. Stimulation of HSPCs in the bone marrow has been shown to lead to functionally altered progenitor cells. We hypothesize that BCG vaccination leads to alterations in the composition and function of the bone marrow, leading to the observed long-term immune modulatory effects of BCG on the innate immune system. Our objective is to examine the effect of BCG vaccination on the composition and function of bone marrow. Participants will be randomised 3:1 to the intervention and the placebo groups, respectively. Main study parameters are comparison of cellular composition of bone marrow and functional assessment of HSPCs in terms of cytokine production and metabolism before and after BCG vaccination. Multiple myeloid progenitor populations will be FACS sorted and mRNA sequenced.