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
Affiliations
Dorcas O. Owusu
Kumasi Centre for Collaborative Research in Tropical Medicine (KCCR), Kumasi 00233, Ghana
Ernest Adankwah
Kumasi Centre for Collaborative Research in Tropical Medicine (KCCR), Kumasi 00233, Ghana
Wilfred Aniagyei
Kumasi Centre for Collaborative Research in Tropical Medicine (KCCR), Kumasi 00233, Ghana
Isaac Acheampong
Kumasi Centre for Collaborative Research in Tropical Medicine (KCCR), Kumasi 00233, Ghana
Difery Minadzi
Kumasi Centre for Collaborative Research in Tropical Medicine (KCCR), Kumasi 00233, Ghana
Augustine Yeboah
Kumasi Centre for Collaborative Research in Tropical Medicine (KCCR), Kumasi 00233, Ghana
Joseph F. Arthur
Kumasi Centre for Collaborative Research in Tropical Medicine (KCCR), Kumasi 00233, Ghana
Millicent Lamptey
Kumasi Centre for Collaborative Research in Tropical Medicine (KCCR), Kumasi 00233, Ghana
Monika M. Vivekanandan
Kumasi Centre for Collaborative Research in Tropical Medicine (KCCR), Kumasi 00233, Ghana
Mohammed K. Abass
Agogo Presbyterian Hospital, Agogo, Ghana
Francis Kumbel
St. Mathias Catholic Hospital, Yeji, Ghana
Francis Osei-Yeboah
Atebubu District Hospital, Atebubu, Ghana
Amidu Gawusu
Sene West Health Directorate, Kwame Danso, Ghana
Linda Batsa Debrah
Kumasi Centre for Collaborative Research in Tropical Medicine (KCCR), Kumasi 00233, Ghana
Alexander Debrah
Kumasi Centre for Collaborative Research in Tropical Medicine (KCCR), Kumasi 00233, Ghana
Ertan Mayatepek
Department of General Pediatrics, Neonatology and Pediatric Cardiology, Medical Faculty, University Hospital Duesseldorf, Heinrich-Heine University, 40225 Duesseldorf, Germany
Julia Seyfarth
Department of General Pediatrics, Neonatology and Pediatric Cardiology, Medical Faculty, University Hospital Duesseldorf, Heinrich-Heine University, 40225 Duesseldorf, Germany
Richard O. Phillips
Kumasi Centre for Collaborative Research in Tropical Medicine (KCCR), Kumasi 00233, Ghana
Marc Jacobsen
Department of General Pediatrics, Neonatology and Pediatric Cardiology, Medical Faculty, University Hospital Duesseldorf, Heinrich-Heine University, 40225 Duesseldorf, Germany
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.
