300BCG

The aim of this project is to elucidate the host and environmental factors that influence the magnitude of
the individual trained immunity responses to BCG vaccination using a systems biology approach.

The Bacillus Calmette-Guérin (BCG) vaccine not only protects against infection with Mycobacterium tuberculosis and Mycobacterium leprae, but has also been shown to induce protection against a large number of unrelated pathogens. The non-specific effects of BCG lead to significant reduced infant morbidity and mortality. These striking effects are most likely mediated by the enhanced release of monocyte-derived cytokines resulting from epigenetic reprogramming of innate immune cells by BCG, a process that has been called trained immunity. However, the factors that influence the individual response to BCG vaccination remain largely unknown. A better understanding of the mechanisms involved is crucial in order to find ways to enhance innate immunological memory and could lead to the development of new vaccines and therapeutics.

Study design

The intervention trial was performed at the Radboudumc. After screening and obtaining informed consent, blood was drawn by venipuncture before, 2 weeks and 3 months after vaccination. In addition, at these three time points gut and oral microbiome samples were collected and volunteers are asked to complete a questionnaire.

Primary Outcomes

1) Immune cell function:

– ex vivo cytokine responses of monocytes

– immunophenotype of cell subpopulations

2) Genetic variation

3) Epigenetic, transcription and metabolic profiles relating to immune function of peripheral monocytes

4) Microbiome variation

Secondary Outcomes

1) Metadata (clinical, environmental data)

2) Skin inflammation at vaccination site