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.
Bibliographical noteFunding Information:
This study was supported by a grant from the Basic Science Research Program through the National Research Foundation of Korea (NRF) founded by the Ministry of Science, ICT and Future Planning (NRF-2015K1A3A7A03073714) and from the Korean Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI) founded by the Ministry for Health, Welfare, and Family Affairs, Republic of Korea (HI14C1324). LSHTM and ITRC are partners in a grant under the MRC-KHIDI UK-Korea Partnering Award scheme awarded to HL and SS with Grant No. HI17C0324 and MC_PC_17109 in TBVAC2020 supported by the European Commission under the H2020 program, with Grant No. 643381; the ITRC group was funded by a Grant (NRF-2015K1A3A7A03073714).
Copyright © 2019 Lee, Kim, Kang, Kim, Sim, Zelmer, Fletcher, Dockrell, Smith and Cho.
All Science Journal Classification (ASJC) codes
- Immunology and Allergy