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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.

Author information

1
Division of Clinical Infectious Diseases, Research Center Borstel, Borstel, Germany.
2
German Center for Infection Research (DZIF), Hamburg, Germany.
3
International Health/Infectious Diseases, University of Lübeck, Lübeck, Germany.
4
Division of Microbial Interface Biology, Research Center Borstel, Borstel, Germany.
5
National Reference Center for Mycobacteria, Research Center Borstel, Borstel, Germany.
6
Department of Medicine, Karolinska Institute, Stockholm, Sweden.

Abstract

Background:

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.

Methods:

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.

Results:

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).

Conclusion:

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.

KEYWORDS:

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

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