BCG-induced Epigenetic Modifications in the NEXT Generation

Phase 4Active Not RecruitingNCT05766345

Radboud University Medical Center36 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

SINGLE

Enrollment

Conditions

Trained Immunity BCG Vaccine Epigenetics

Interventions

Eligibility

Sex: MALEMin age: 18 YearsMax age: 25 YearsHealthy volunteers:

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

DNA methylation profile of sperm cells (first comparison; CHANGE)

Differentially methylated regions (DMRs)

Time frame: Comparing T3 to baseline

DNA methylation profile of sperm cells (second comparison; CHANGE)

Differentially methylated regions (DMRs)

Time frame: Comparing T4 to baseline

Secondary Outcomes

Immunological profile of PBMCs, before and after BCG vaccination (comparison; CHANGE)

Cytokine production assays (e.g. TNFa, IL6, IL1b)

Time frame: Comparing T1-T4 to baseline

CHANGE of the epigenetic profile of innate immune cells

Differentially methylated regions (DMRs), ATAC sequencing, RNA sequencing