Short summary

BCG vaccine has non-specific effects which provide protection against other infections. The present project will aim to investigate whether effects of BCG, on the innate immune system, could explain this non-specific protection. This will be done by combining in vitro studies and vaccination trials in healthy volunteers to elucidate the effects of BCG vaccine on the immune system, which might lead to more rational vaccination strategies.

Rationale

BCG vaccine is used to confer protection against tuberculosis. Apart from this specific effect, in observational studies and clinical trials, BCG vaccination has been shown to reduce infant mortality due to infectious diseases such as respiratory infections and neonatal sepsis.

Recently, BCG has been shown to induce epigenetic programming of monocytes, leading to an enhanced pro-inflammatory response of the innate immune system after BCG vaccination, termed trained immunity. Also, several studies show that BCG leads to increased T-cell mediated immunity to non-related pathogens, termed heterologous immunity.

This project will further investigate the effects of BCG vaccination on the innate immune system with the purpose of designing more rational vaccination strategies, for instance by using BCG vaccine to boost the immunological effect of other vaccines such as typhoid fever vaccine and DTP vaccine.

Description of the cohort

The cohorts of this project will consist of healthy adult volunteers, both male and female, who will be vaccinated with BCG vaccine and potentially other vaccines. Most of the cohort will consist of a student population.

Data and biological material

Blood will be isolated before and after vaccination of volunteers. From this several materials will be collected: DNA, serum, plasma, peripheral blood mononuclear cells (PBMCs), supernatants from ex vivo PBMC stimulations, mRNA from ex vivo PBMC stimulations, and chromatin.

Questionnaire data will be collected regarding overall health status of participants, and side-effects of vaccination.

Collaborating researchers and departments

Research Center for Vitamins and Vaccines (CVIVA), Bandim Health Project, the State Serum Institute, Copenhagen

• Professor C.S. Benn, MD, Phd

Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands

• Professor M.G. Netea
• Dr., R. van Crevel
• Dr., R.J.W. Arts, MD

Publications associated with the project

Long-term in vitro and in vivo effects of ?-irradiated BCG on innate and adaptive immunity. / Arts, R. J. W., Blok, B. A., Aaby, P., Joosten, L. A. B., de Jong, D., van der Meer, J. W. M., Benn, C. S., van Crevel, R. & Netea, M. G. 2015 I: Journal of Leukocyte Biology. 98, 6, s. 995-1001

Trained innate immunity as underlying mechanism for the long-term, nonspecific effects of vaccines. / Blok, B. A., Arts, R. J. W., van Crevel, R., Benn, C. S. & Netea, M. G. sep. 2015 I: Journal of Leukocyte Biology. 98, 3  

Variation of growth in the production of the BCG vaccine and the association with the immune response. An observational study within a randomised trial. / Biering-Sørensen, S., Jensen, K. J., Aamand, S. H., Blok, B., Andersen, A., Monteiro, I., Netea, M. G., Aaby, P., Benn, C. S. & Hasløv, K. R. 21 apr. 2015 I: Vaccine. 33, 17  

Vitamin A induces inhibitory histone methylation modifications and down-regulates trained immunity in human monocytes. / Arts, R. J. W., Blok, B. A., van Crevel, R., Joosten, L. A. B., Aaby, P., Benn, C. S. & Netea, M. G. jul. 2015 I: Journal of Leukocyte Biology. 98, 1