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

Article scientifique 2020 Anglais

Résumé

Abstract We characterize the breadth, function and phenotype of innate and adaptive cellular responses in a prevention ofMycobacterium tuberculosisinfection 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 unexpected NKTlikesubset, 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 sustainedMycobacterium tuberculosisinfection, modulates multiple immune cell subsets, in particular conventional Th1 and Th22 cells, which should be investigated in discovery studies of correlates of protection.

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Rozot, V., Nemes, E., Geldenhuys, H., Musvosvi, M., Toefy, A., Rantangee, F., Makhethe, L., Erasmus, M., Bilek, N., Mabwe, S., Finak, G., Fulp, W., Ginsberg, A., Hokey, D., Shey, M., Gurunathan, S., DiazGranados, C., Bekker, L., Hatherill, M., Scriba, T., Abrahams, C., Aderiye, M., Africa, H., Albertyn, D., Alexander, F., Amsterdam, J., Andersen, P., Arendsen, D., Bester, H., Beyers, E., Botes, N., Botes, J., Braaf, S., Brooks, R., Cloete, Y., Companie, A., Croucher, K., Davids, I., Bruyn, G., Diamond, B., Dlakavu, P., Dolo, P., Dubel, S., Elbring, C., Ellis, R., Erasmus, M., Esterhuizen, T., Evans, T., Fattore, C., Gelderbloem, S., Gempies, D., Goliath, S., Gomes, P., Gregg, Y., Hamilton, E., Hanekom, W., Hector, J., Herling, R., Herselman, Y., Hopkins, R., Hughes, J., Hunt, D., Issel, H., Janosczyk, H., Jaxa, L., Jones, C., Kassiem, J., Keffers, S., Kelepu, X., Keyser, A., Kieffer, A., Kromann, I., Krüger, S., Lambrick, M., Landry, B., Langata, P., Lempicki, M., Locas, M., Luabeya, A., Mactavie, L., Makunzi, L., Mangala, P., Maqubela, C., Mosito, B., Mouton, A., Mulenga, H., Mullins, M., Noble, J., Nombida, O., O’Dee, D., O’Neil, A., Ockhuis, R., Omarjee, S., Opperman, F., Patel, D., Petersen, C., Pretorius, A., Pretorius, D., Raine, M. (2020). Multidimensional analyses reveal modulation of adaptive and innate immune subsets by tuberculosis vaccines. https://doi.org/10.1038/s42003-020-01288-3

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Auteur(s)

Virginie Rozot Elisa Nemes Hennie Geldenhuys Munyaradzi Musvosvi Asma Toefy Frances Rantangee Lebohang Makhethe Mzwandile Erasmus Nicole Bilek Simbarashe Mabwe Greg Finak William J. Fulp Ann M. Ginsberg David A. Hokey Muki Shey Sanjay Gurunathan Carlos A. DiazGranados Linda‐Gail Bekker Mark Hatherill Thomas J. Scriba Charmaine Abrahams Marcelene Aderiye Hadn Africa Deidre Albertyn Fadia Alexander Julia Amsterdam Peter Andersen Denis Arendsen H. Bester Elizabeth Beyers Natasja Botes Janelle Botes Samentra Braaf Roger A. Brooks Yolundi Cloete Alessandro Companie Kristin Croucher Ilse Davids Guy de Bruyn Bongani Diamond Portia Dlakavu Palesa Dolo Sahlah Dubel Cindy Elbring Ruth D. Ellis Margareth Erasmus Terence Esterhuizen Thomas G. Evans Christine Fattore Sebastian Gelderbloem Diann Gempies Sandra Goliath Peggy Gomes Yolande Gregg Elizabeth Hamilton Willem A. Hanekom Johanna Hector Roxanne Herling Yulandi Herselman Robert Hopkins Jane Hughes Devin J Hunt Henry Issel Helene Janosczyk Lungisa Jaxa Carolyn Jones Jateel Kassiem Sophie Keffers Xoliswa Kelepu Alana Keyser Alexia Kieffer Ingrid Kromann Sandra Krüger Maureen Lambrick Bernard Landry Phumzile Langata Maria Lempicki Marie-Christine Locas Angelique Kany Kany Luabeya Lauren Mactavie Lydia Makunzi Pamela Mangala Clive Maqubela Boitumelo Mosito Angelique Mouton Humphrey Mulenga Mariana Mullins Julia Noble Onke Nombida Dawn M. O’Dee Amy O’Neil Rose Ockhuis Saleha Omarjee Fajwa Opperman Dhaval M. Patel Christel Petersen Abraham Pretorius Debbie Pretorius Michael Raine

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