Immune repons induced by vaccination with BCG

Tuberculosis is a growing global health problem. The only available vaccine is
bacille calmette-guérin (BCG). Each year BCG is given to millions of childeren
around the world, particularly in tuberculosis endemic countries. It protects
young childeren from severe forms of tuberculosis, but it is of limited value
in adults. We hypothesize that the antigen expression profile of BCG during
intradermal vaccination is different from that of Mycobacterium tuberculosis.
The partial failure of BCG may be related to this difference.

Primary objective is to characterize the anti-mycobacterial immune responses
during vaccination with live-attenuated M. Bovis BCG Danish strain 1331, in
order to provide a framework for using biomarkers in future TB vaccine trials.
Secondary objective is to evaluate whether biomarkers, specific for BCG can be
detected in the circulation and in the urine following vaccination. Such
profiles could be useful as markers in future TB vaccine trials and may also be
a first step in developing these techniques to diagnose latent tuberculosis
infection.

Healthy adult individuals will be vaccinated with BCG and temporal changes in T
cell responses against mycobacterial antigens will be monitored in vitro. The
research will be conducted by the department of Infectious Diseases at the
Leiden University Medical Center.

BCG vaccine SSI (Danish strian 1331; RVG number 17661)

Burden for study participants:
The total average duration of the visits to the study centrum (LUMC) is
approximately 4 hours, divided over 10 visits over a period of 52 weeks. During
the visits two tuberculin skintest will be performed, one vaccination with BCG
and 9 vena punctures will be perfomed in which participants will be required to
donate a maximum of 52.5 ml of venous blood per visit, a total of 448 ml of
venous blood during the entire study and 5 urine samples for the laboratory
analyses.

Potential risks: BCG is a registered vaccine which is widely used throughout
the world. It is a live-attenuated vaccine and is contraindicated for persons
with impaired cellular immunity. In view of our outcome measures BCG will also
not be given to persons with a positive tuberculin reaction or a positive
Quantiferon-TB Gold In-Tube blood test. In case of a positive Mantoux test
and/or Quantiferon-Tb Gold In-Tube test at week-1, the subject will be
counseled by the investigator. The "Tuberculosebestrijding of GGD Hollands
Midden"will be contacted. If the investigator and/or the GGD think it
necessary, the participant will be refered to this department for further
counseling and management.