We hypothesize that BCG vaccination leads to alterations in the composition and function of the bone marrow, leading to the observed long-term immunolomodulatory effects of BCG on the innate immune system.
ID
Bron
Verkorte titel
Aandoening
Non specific effects of vaccines, ex-vivo cytokine responses, trained innate immunity.
Niet specifieke effecten vaccinatie, ex-vivo cytokine responsen, getrainde aangeboren immuniteit
Ondersteuning
Onderzoeksproduct en/of interventie
Uitkomstmaten
Primaire uitkomstmaten
- Cellular composition of bone marrow compartment by FACS<br>
- Ex-vivo cytokine (IL-1â, TNF, IL-6, IL-10, IFNã) release of full bone marrow aspirate, PBMCs, CD34+ cell fraction and bone marrow derived macrophages upon stimulation with PAMPs (e.g. LPS) and pathogens (e.g. S. aureus, C. albicans, M. tuberculosis, S. pneumonia)<br>
Secondary study parameters
Achtergrond van het onderzoek
BCG vaccination is associated with non specific beneficial effects, leading to decreased childhood mortality in countries with high infectious disease burden. A possible immunological mechanism causing these non specific effects is BCG induced trained immunity. BCG vaccination leads to epigenetic modifications in innate immune cells, resulting in an enhenced cytokine respons after restimulation with a non-specific pathogen.
These effects last for up to one year. A hypothesis explaining the longevity of these effects is that BCG could induce alterations in hematopoeitic stem and progenitor cells.
Doel van het onderzoek
We hypothesize that BCG vaccination leads to alterations in the composition and function of the bone marrow, leading to the observed long-term immunolomodulatory effects of BCG on the innate immune system.
Onderzoeksopzet
Baseline (T0)
Two weeks (Tw2)
Three months (Tm3)
Onderzoeksproduct en/of interventie
BCG vaccination
Publiek
L.C.J. de Bree
Geert Grooteplein Zuid 10,
Nijmegen 6525 GA
The Netherlands
Charlotte.debree@radboudumc.nl
Wetenschappelijk
L.C.J. de Bree
Geert Grooteplein Zuid 10,
Nijmegen 6525 GA
The Netherlands
Charlotte.debree@radboudumc.nl
Belangrijkste voorwaarden om deel te mogen nemen (Inclusiecriteria)
- Written informed consent
- Age ¡Ý18
- Healthy
Belangrijkste redenen om niet deel te kunnen nemen (Exclusiecriteria)
- Use of systemic medication other than oral anti-contraceptive drugs
- Vaccination within 3 months prior to study period
- History of haematological disease
- History of malignancy
- Medical history of disease associated with immune deficiency
- Previous BCG vaccination
- Acute illness within 2 months prior to start of study
- Pregnancy
- Anaemia or other deviations in a complete blood count
- NSAID within the last 2 weeks
- History of claustrophobia
- Fastened glucose > 8 mmol/l
Opzet
Deelname
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