Abstract
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.
Highlights
Pulmonary tuberculosis (TB) is an airborne infectious disease caused by Mycobacterium tuberculosis (Mtb), which is a significant burden for the world, reaching 9.6 million new TB cases and 1.5 million deaths per year [1]
With continuous efforts to overcome the hurdles for effective TB vaccine development including the absence of a predictive animal model or validated correlates of protection, we need to prioritize vaccine candidates that would be effective across the entire spectrum of TB infection ranging from latent TB infection (LTBI) to active TB disease
The data shows that other general characteristics of the participants including gender and presence of a Bacillus Calmette-Guérin (BCG) scar did not affect the result of the QuantiFERON-TB R Gold In-tube assay (QFT)-GIT test (Table 1)
Summary
Pulmonary tuberculosis (TB) is an airborne infectious disease caused by Mycobacterium tuberculosis (Mtb), which is a significant burden for the world, reaching 9.6 million new TB cases and 1.5 million deaths per year [1]. BCG vaccine efficacy varies widely (from 0 to 80%) between geographical locations, with demographical characteristics, and with the socio-economic status of the populations [8, 9]. With this partial protective efficacy of BCG in humans, it is important to introduce novel TB vaccine candidates that will work for all ages, regions, and regardless of the HIV epidemic, along with improvement of rapid diagnosis and effective drug treatments. In this study we investigated the long-term immunity induced by childhood BCG vaccination and 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
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