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.
ID
Source
Brief title
Condition
- Immunodeficiency syndromes
- Hepatobiliary neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
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 outcome
- Metadata (clinical, environmental data)
- Skin inflammation at vaccination site
Background summary
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 objective
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.
Study design
The intervention trial will be performed at the Radboudumc. 300 Healthy
volunteers (equal numbers of females and males) will be recruited to receive a
vaccination with BCG. After screening and obtaining informed consent, blood
will be drawn by venipuncture before, 2 weeks and 3 months after vaccination.
In addition, at these three time points gut and oral microbiome samples will be
collected and volunteers are asked to complete a questionnaire.
Intervention
BCG vaccine.
Study burden and risks
BCG vaccine is the most used human vaccine in the world, with an excellent
track record of safety.
Potential risks include only the side effects of the vaccine, of which
localized skin reactions are most common. The local reaction after BCG
vaccination is usually mild and self-limiting. Less common are fever and
headache after vaccination and if they occur they are typically mild.
Enlargement of the axillary lymph nodes may occasionally occur after
vaccination but will usually regress spontaneously after a few months.
Local haematoma formation could occur at the site of vena puncture. Both
vaccination and vena puncture will only be performed by experienced personnel
in this study.
Apart from protection against extrapulmonary infection with Mycobacterium
tuberculosis and against leprosy, there are no expected benefits for
participants in the study. However, findings may show new mechanisms
responsible for the non-specific effects of vaccination and this may lead to
novel strategies to optimize vaccination programs.
Geert Grooteplein Zuid 10
Nijmegen 6525 GA
NL
Geert Grooteplein Zuid 10
Nijmegen 6525 GA
NL
Listed location countries
Age
Inclusion criteria
Age>18
Healthy
Exclusion criteria
Use of chronic or acute medication during the last month before the study other than oral anti-contraceptive drugs
Vaccination within 3 months prior to study period
Medical history of disease associated with immune deficiency
Previous BCG vaccination
Contact with tuberculosis patients or born in a tuberculosis endemic country
Acute (febrile) illness within 4 weeks prior to start of study
Pregnancy
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL58553.091.16 |