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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Immunol. | doi: 10.3389/fimmu.2019.00896

In vitro mycobacterial growth inhibition in South Korean adults with latent TB infection

 Hyejon Lee1, 2*, Jungho Kim1,  Young Ae Kang3, Deok Ryun Kim4, Bora Sim2, Andrea Zelmer5,  Helen A. Fletcher5,  Hazel M. Dockrell5,  Steven G. Smith5 and Sang-Nae Cho1
  • 1International Tuberculosis Research Center, South Korea
  • 2Department of Microbiology, Institute for Immunology and Immunological Disease, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, South Korea
  • 3Institute of Chest Diseases, Yonsei University College of Medicine, South Korea
  • 4Development and Delivery Unit, International Vaccine Institute, South Korea
  • 5Department of Immunology and Infection, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, United Kingdom

Background: It is important to understand the ability to inhibit mycobacterial growth in healthy adults who would have been Bacillus Calmette-Guérin (BCG) vaccinated in childhood as this group will be the potential target population for novel booster TB vaccine trials. In this study we investigated not only the long-term immunity induced by childhood BCG vaccination but also protective immunity in terms of the ability to inhibit mycobacterial growth in those who were BCG vaccinated in childhood, with evidence of recent or remote TB infection.

Methods: We measured the baseline immune response using a functional mycobacterial growth inhibition assay (MGIA) as a novel approach and an intracellular cytokine staining (ICS) assay as a reference approach in healthy adults, with different status of Mycobacterium tuberculosis (Mtb) infection.

Results: Based on MGIA responses in historically BCG-vaccinated healthy adults, demographical characteristics including age and gender did not affect mycobacterial growth inhibition in PBMC. However, the uninfected healthy control (HC) group showed a greater ability to inhibit mycobacterial growth compared with the latent TB infection (LTBI) group (P = 0.0005). In terms of the M.tuberculosis antigen-specific T-cell immune response in diluted whole blood quantitated using an ICS assay, the LTBI group had a higher frequency of polyfunctional CD 4+ T cells compared with the HC group (P = 0.0002), although there was no correlation between ICS and the MGIA assay.

Conclusion: The Mtb infection status had a significant impact on mycobacterial growth inhibition in PBMC from healthy adults in South Korea, a country with an intermediate burden of tuberculosis, with healthy controls showing the greatest mycobacterial growth inhibition.

Keywords: Mycobacterial growth inhibition, correlates, Vaccine, Tuberculosis, latent tuberculosis infection

Received: 19 Nov 2018; Accepted: 08 Apr 2019.

Edited by:

Juraj Ivanyi, King's College London, United Kingdom

Reviewed by:

Katalin A. Wilkinson, Francis Crick Institute, United Kingdom
Utpal Sengupta, The Leprosy Mission Trust India, India  

Copyright: © 2019 Lee, Kim, Kang, Kim, Sim, Zelmer, Fletcher, Dockrell, Smith and Cho. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: PhD. Hyejon Lee, International Tuberculosis Research Center, Changwon, South Korea, hyejonlee@yuhs.ac