Adolescent BCG revaccination induces a phenotypic shift in CD4 T cell responses to Mycobacterium tuberculosis.

Adolescent BCG revaccination induces a phenotypic shift in CD4 T cell responses to Mycobacterium tuberculosis.

Publication date: Jun 18, 2024

A recent clinical trial demonstrated that Bacille Calmette-GucE9rin (BCG) revaccination of adolescents reduced the risk of sustained infection with Mycobacterium tuberculosis (M. tb). In a companion phase 1b trial, HVTN 602/Aeras A-042, we characterize in-depth the cellular responses to BCG revaccination or to a H4:IC31 vaccine boost to identify T cell subsets that could be responsible for the protection observed. High-dimensional clustering analysis of cells profiled using a 26-color flow cytometric panel show marked increases in five effector memory CD4 T cell subpopulations (T) after BCG revaccination, two of which are highly polyfunctional. CITE-Seq single-cell analysis shows that the activated subsets include an abundant cluster of Th1 cells with migratory potential. Additionally, a small cluster of Th17 T cells induced by BCG revaccination expresses high levels of CD103; these may represent recirculating tissue-resident memory cells that could provide pulmonary immune protection. Together, these results identify unique populations of CD4 T cells with potential to be immune correlates of protection conferred by BCG revaccination.

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Concepts Keywords
Calmette Adolescent
Cd103 BCG Vaccine
Mycobacterium BCG Vaccine
Tuberculosis CD4-Positive T-Lymphocytes
Vaccine Female
Humans
Immunization, Secondary
Immunologic Memory
Male
Mycobacterium tuberculosis
Phenotype
Single-Cell Analysis
Th1 Cells
Tuberculosis

Semantics

Type Source Name
drug DRUGBANK BCG vaccine
pathway REACTOME Infection with Mycobacterium tuberculosis
disease MESH infection
drug DRUGBANK Tretamine
disease MESH tuberculosis
pathway KEGG Tuberculosis
disease MESH Morbidity
disease MESH Infectious Diseases
drug DRUGBANK Creatinolfosfate

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