AUTHOR=Radloff Juliane , Heyckendorf Jan , van der Merwe Lize , Sanchez Carballo Patricia , Reiling Norbert , Richter Elvira , Lange Christoph , Kalsdorf Barbara 

TITLE=Mycobacterium Growth Inhibition Assay of Human Alveolar Macrophages as a Correlate of Immune Protection Following Mycobacterium bovis Bacille Calmette–Guérin Vaccination

JOURNAL=Frontiers in Immunology

VOLUME=9

YEAR=2018

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2018.01708

DOI=10.3389/fimmu.2018.01708

ISSN=1664-3224

ABSTRACT=<sec id="ST1"><title>Background</title><p>In order to eliminate tuberculosis (TB), an effective vaccine is urgently needed to prevent infection with <italic>Mycobacterium tuberculosis</italic>. A key obstacle for the development of novel TB vaccines is the lack of surrogate markers for immune protection against <italic>M. tuberculosis</italic>.</p></sec><sec id="ST2"><title>Methods</title><p>We investigated growth rates of <italic>M. tuberculosis</italic> 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 <italic>Mycobacterium bovis</italic> Bacille Calmette–Guérin (BCG) of healthy adult volunteers.</p></sec><sec id="ST3"><title>Results</title><p>Vaccination induced a positive response (<italic>p</italic> &lt; 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 <italic>M. bovis</italic> BCG-vaccination revealed no significant difference in time to culture positivity before and after vaccination in BALC (<italic>p</italic> = 0.604) and PBMC (<italic>p</italic> = 0.199). The magnitude of the PPD-response induced by <italic>M. bovis</italic> BCG-vaccination did not correlate with growth control in BALC and PBMC (correlation = 0.468, 95% CI: −0.016 to 0.775).</p></sec><sec id="ST4"><title>Conclusion</title><p>In conclusion, <italic>M. bovis</italic> BCG-vaccination-induced mycobacterial-specific cytokine immune response does not result in functional immune control against <italic>M. tuberculosis</italic> in the MGIA.</p></sec>