The objective of the study is to determine the effect of BCG revaccination and high dose BCG vaccination on the induction and course of innate immune memory.
ID
Source
Brief title
Condition
- Immune disorders NEC
- Ancillary infectious topics
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
1. To assess the function of monocytes measured by cytokine responses after
stimulation with unrelated antigens at different timepoints
a. before and after single standard BCG vaccination
b. before and after BCG revaccination
c. before and after high dose BCG vaccination
2. To compare cytokine responses at different timepoints
a. Between standard single dose vaccination and revaccination
b. Between standard single dose vaccination and high dose vaccination.
3. To compare transcription and epigenetic profiles of monocytes before and
after BCG (re)vaccination.
Secondary outcome
Identifying SNP variants of genes relevant for innate immune function.
Cellular metabolism of peripheral monocytes
Background summary
The live attenuated vaccine Bacillus Calmette-Guérin is able to induce
non-specific beneficial effects by protection against non related infectious
diseases beyond its target disease via epigenetic modifications. However, the
effect of BCG on innate immune responses wanes after three months. The
development of methods to boost the effect of BCG induced trained immunity will
be of great value. This study will investigate the effect of BCG revaccination,
as well as high dose BCG vaccination on the induction and course of trained
immunity in healthy volunteers.
Study objective
The objective of the study is to determine the effect of BCG revaccination and
high dose BCG vaccination on the induction and course of innate immune memory.
Study design
This study will be a randomized placebo controlled trial. 50 healthy
volunteers, aged 18-55 years, previously BCG-unvaccinated, will be randomized
to receive a BCG vaccination followed by a second BCG vaccination (group 1, n=
15), placebo vaccination (vaccine diluents) followed by high dose BCG (group 2,
n = 15), placebo vaccination followed by standard dose BCG (group 3, n=15).,
or placebo vaccination (twice) with an interval of three months (group 4 n = 5)
Throughout the study, blood will be drawn for ex vivo restimulations at
different time points to analyze changes in immune responses after BCG
vaccination. The study period will last for 6 months. Measuremens will be
performed in a blinded manner.
Intervention
Group 1: standard dose BCG + standard dose BCG (0,1 ml intracuteneous injection
of BCG vaccin (SSI, AJ vaccines) 0.75 mg/ml)
Group 2: placebo + high dose BCG (0,1 ml intracuteneous injection of BCG vaccin
(SSI, AJ vaccines), 1,5 mg/ml)
Group 3: placebo + standard dose BCG (0,1 ml intracuteneous injection of BCG
vaccin (SSI, AJ vaccines), 0.75 mg/ml)
Group 4: placebo + placebo
Study burden and risks
There will be no particular benefit for participants. BCG vaccination is safe
in healthy volunteers and only mild side reactions like headache or fever occur
in 1 % -0.1% of vaccinated persons. BCG vaccination will result in a small scar
at vaccination site. BCG vaccination can interfere with future tuberculin skin
test for tuberculosis, by causing a false positive tuberculin skin test
(Mantoux test). In case of future need of screening for latent tuberculosis,
BCG vaccinated volunteers should be advised to be screened by other available
methods, like chest x-ray or in vitro interferon gamma release assay.
Geert Grooteplein-Zuid 10
Nijmegen 6525 GA
NL
Geert Grooteplein-Zuid 10
Nijmegen 6525 GA
NL
Listed location countries
Age
Inclusion criteria
Healthy.
Age between 18 and 55 years old.
Exclusion criteria
Medical history associated with immunological deficiency.
History of BCG vaccination.
Chronic use of systemic drugs other than oral contraceptives.
Use of NSAIDS less than 4 weeks prior to the start of the study.
For female subjects: a positive pregnancy test at screening.
Receipt of vaccination 3 months prior to the start of the study or plans to
receive any other vaccination during the study period
Acute illness two weeks prior to the start of the study.
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 | NL58219.091.16 |