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Front Immunol. 2018 Jul 24;9:1708. doi: 10.3389/fimmu.2018.01708. eCollection 2018.

Mycobacterium Growth Inhibition Assay of Human Alveolar Macrophages as a Correlate of Immune Protection Following Mycobacterium bovis Bacille Calmette-Guérin Vaccination.

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Division of Clinical Infectious Diseases, Research Center Borstel, Borstel, Germany.
German Center for Infection Research (DZIF), Hamburg, Germany.
International Health/Infectious Diseases, University of Lübeck, Lübeck, Germany.
Division of Microbial Interface Biology, Research Center Borstel, Borstel, Germany.
National Reference Center for Mycobacteria, Research Center Borstel, Borstel, Germany.
Department of Medicine, Karolinska Institute, Stockholm, Sweden.



In order to eliminate tuberculosis (TB), an effective vaccine is urgently needed to prevent infection with Mycobacterium tuberculosis. A key obstacle for the development of novel TB vaccines is the lack of surrogate markers for immune protection against M. tuberculosis.


We investigated growth rates of M. tuberculosis in the mycobacterial growth inhibition assay (MGIA) as a marker for mycobacterial growth control of human bronchoalveolar lavage (BALC) and peripheral blood mononuclear cells (PBMC) before and after vaccination with Mycobacterium bovis Bacille Calmette-Guérin (BCG) of healthy adult volunteers.


Vaccination induced a positive response (p < 0.001) to purified protein derivate (PPD) in 58.8% of the individuals in an interferon-γ release assay-ELISpot. Intraindividual evaluation of the MGIA growth rates before and after M. bovis BCG-vaccination revealed no significant difference in time to culture positivity before and after vaccination in BALC (p = 0.604) and PBMC (p = 0.199). The magnitude of the PPD-response induced by M. bovis BCG-vaccination did not correlate with growth control in BALC and PBMC (correlation = 0.468, 95% CI: -0.016 to 0.775).


In conclusion, M. bovis BCG-vaccination-induced mycobacterial-specific cytokine immune response does not result in functional immune control against M. tuberculosis in the MGIA.


Bacille Calmette–Guérin; interferon-γ release assay immune response; mycobacterial growth inhibition assay; tuberculosis; vaccine; vitamin D

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