Abstract
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.
Highlights
Tuberculosis (TB) is a leading cause of morbidity and mortality worldwide [1]
We evaluated the performance of the mycobacterial growth inhibition assay (MGIA) as a marker for immune protection following M. bovis Bacillus CalmetteGuérin (BCG)-vaccination of healthy adult volunteers
M. bovis BCG-vaccination did not have a significant impact on the mycobacterial growth rate in bronchoalveolar lavage cells (BALCs) or peripheral blood mononuclear cells (PBMC) and M. bovis BCG-induced T-cell immune response did not correlate with the mycobacterial growth rate in pulmonary or systemic mononuclear cells
Summary
Tuberculosis (TB) is a leading cause of morbidity and mortality worldwide [1]. In the year 2016, the World Health Organization reported 10.4 million new cases of TB. Immune Responses After BCG-Vaccination that are latently infected with Mycobacterium tuberculosis (LTBI) and most effectively by a preventive vaccine. Almost 100 years ago, Albert Calmette and Camille Guérin developed a vaccine based on attenuated Mycobacterium bovis [Bacillus CalmetteGuérin (BCG)], which is still the only available anti-TB vaccine in clinical use today [2, 3]. M. bovis BCG is among the most commonly used of all vaccines worldwide, its effect is largely on the attenuation of severe forms of the disease in children and it does not prevent TB in adults [4, 5]. 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
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