Multidimensional analyses reveal modulation of adaptive and innate immune subsets by tuberculosis vaccines

Virginie Rozot, The C-040-404 Study Team, Elisa Nemes, Hennie Geldenhuys, Munyaradzi Musvosvi, Asma Toefy, Frances Rantangee, Lebohang Makhethe, Mzwandile Erasmus, Nicole Bilek, Simbarashe Mabwe, Greg Finak (+9 others)
2020 Communications Biology  
We characterize the breadth, function and phenotype of innate and adaptive cellular responses in a prevention of Mycobacterium tuberculosis infection trial. Responses are measured by whole blood intracellular cytokine staining at baseline and 70 days after vaccination with H4:IC31 (subunit vaccine containing Ag85B and TB10.4), Bacille Calmette-Guerin (BCG, a live attenuated vaccine) or placebo (n = ~30 per group). H4:IC31 vaccination induces Ag85B and TB10.4-specific CD4 T cells, and an
more » ... ed NKTlike subset, that expresses IFN-γ, TNF and/or IL-2. BCG revaccination increases frequencies of CD4 T cell subsets that either express Th1 cytokines or IL-22, and modestly increases IFNγ-producing NK cells. In vitro BCG re-stimulation also triggers responses by donor-unrestricted T cells, which may contribute to host responses against mycobacteria. BCG, which demonstrated efficacy against sustained Mycobacterium tuberculosis infection, modulates multiple immune cell subsets, in particular conventional Th1 and Th22 cells, which should be investigated in discovery studies of correlates of protection.
doi:10.1038/s42003-020-01288-3 pmid:33037320 fatcat:hq5tw5qucfd5fiaztpsmr3d4ue