BCG Vaccine, Epigenetics, Trained Immunity
Conditions
Brief summary
Non-specific protective effects resulting from the BCG vaccine appear to be paternally inheritable. Since the BCG vaccine is known to induce trained immunity, epigenetics might explain the fathers' contribution to the immune profile of their offspring. Epigenetic inheritance in mice has recently been demonstrated, but is not established in humans yet. By studying the DNA methylation profile of sperm cells after BCG vaccination, we aim to gain insight into the possibility of epigenetic inheritance in human males.
Interventions
BIOLOGICALBCG-Vaccine SSI [Statens Serum Institut]) Danish strain 1331
Nothing to add
BIOLOGICALPlacebo
Nothing to add
Sponsors
Radboud University Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
MALE
Age
18 Years to 25 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy * Male * Age 18-25 years (at the moment of trial start)
Exclusion criteria
* Any systemic disease or conditin, or the use of systemic medication (with the exception of non-threatening alelrgies, e.g. hay fever) * Smoking or drug use * Prior BCG vaccination * Other vaccination four weeks prior to trial start or four weeks after the first study visit (no vaccine in the same arm as the BCG vaccine for three months) * Acute illness two weeks prior to trial start * Known allergy or history of anaphylaxis/other serious adverse reaction to any vaccine * Participation in another drug trial * Legally incapacitated or unwilling to provide informed consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| DNA methylation profile of sperm cells (first comparison; CHANGE) | Comparing T3 to baseline | Differentially methylated regions (DMRs) |
| DNA methylation profile of sperm cells (second comparison; CHANGE) | Comparing T4 to baseline | Differentially methylated regions (DMRs) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Immunological profile of PBMCs, before and after BCG vaccination (comparison; CHANGE) | Comparing T1-T4 to baseline | Cytokine production assays (e.g. TNFa, IL6, IL1b) |
| CHANGE of the epigenetic profile of innate immune cells | Comparing T1-T4 to baseline | Differentially methylated regions (DMRs), ATAC sequencing, RNA sequencing |
Countries
Netherlands
Outcome results
None listed