Vaccines (Apr 2023)

BCG-Vaccinated Children with Contact to Tuberculosis Patients Show Delayed Conversion of <i>Mycobacterium tuberculosis</i>-Specific IFN-γ Release

  • Dorcas O. Owusu,
  • Ernest Adankwah,
  • Wilfred Aniagyei,
  • Isaac Acheampong,
  • Difery Minadzi,
  • Augustine Yeboah,
  • Joseph F. Arthur,
  • Millicent Lamptey,
  • Monika M. Vivekanandan,
  • Mohammed K. Abass,
  • Francis Kumbel,
  • Francis Osei-Yeboah,
  • Amidu Gawusu,
  • Linda Batsa Debrah,
  • Alexander Debrah,
  • Ertan Mayatepek,
  • Julia Seyfarth,
  • Richard O. Phillips,
  • Marc Jacobsen

DOI
https://doi.org/10.3390/vaccines11040855
Journal volume & issue
Vol. 11, no. 4
p. 855

Abstract

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Mycobacterium (M.) bovis BCG vaccination is recommended for healthy babies after birth in several countries with a high prevalence of tuberculosis, including Ghana. Previous studies showed that BCG vaccination prevents individuals from developing severe clinical manifestations of tuberculosis, but BCG vaccination effects on the induction of IFN-γ after M. tuberculosis infection have hardly been investigated. Here, we performed IFN-γ-based T-cell assays (i.e., IFN-γ Release Assay, IGRA; T-cell activation and maturation marker assay, TAM-TB) in children who had contact with index tuberculosis patients (contacts). These contacts were classified as either being BCG vaccinated at birth (n = 77) or non-BCG-vaccinated (n = 17) and were followed up at three timepoints for a period of one year to determine immune conversion after M. tuberculosis exposure and potential infection. At baseline and month 3, BCG-vaccinated contacts had significantly lower IFN-γ levels after stimulation with M. tuberculosis-specific proteins as compared to non-BCG-vaccinated contacts. This resulted in decreased proportions of positive IGRA results (BCG-vaccinated: 60% at baseline, 57% at month 3; non-BCG-vaccinated: 77% and 88%, respectively) at month 3. However, until month 12, immune conversion in BCG-vaccinated contacts led to balanced proportions in IGRA responders and IFN-γ expression between the study groups. TAM-TB assay analyses confirmed higher proportions of IFN-γ-positive T-cells in non-BCG-vaccinated contacts. Low proportions of CD38-positive M. tuberculosis-specific T-cells were only detected in non-BCG-vaccinated contacts at baseline. These results suggest that BCG vaccination causes delayed immune conversion as well as differences in the phenotype of M. tuberculosis-specific T-cells in BCG-vaccinated contacts of tuberculosis patients. These differences are immune biomarker candidates for protection against the development of severe clinical tuberculosis manifestations.

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