Multidimensional analyses reveal modulation of adaptive and innate immune subsets by tuberculosis vaccines
Authors: Rozot Virginie , Nemes Elisa , Geldenhuys Hennie , Musvosvi Munyaradzi , Toefy Asma , Rantangee Frances , Makhethe Lebohang , Erasmus Mzwandile , Bilek Nicole , Mabwe Simbarashe , Finak Greg , Fulp William , Ginsberg Ann M. , Hokey David A. , Shey Muki , Gurunathan Sanjay , DiazGranados Carlos , Bekker Linda-Gail , Hatherill Mark , Scriba Thomas J. ,   The C-040-404 Study Team, Abrahams Charmaine , Aderiye Marcelene , Africa Hadn , Albertyn Deidre , Alexander Fadia , Amsterdam Julia , Andersen Peter , Arendsen Denis , Bester Hanlie , Beyers Elizabeth , Botes Natasja , Botes Janelle , Braaf Samentra , Brooks Roger , Cloete Yolundi , Companie Alessandro , Croucher Kristin , Davids Ilse , de Bruyn Guy , Diamond Bongani , Dlakavu Portia , Dolo Palesa , Dubel Sahlah , Elbring Cindy , Ellis Ruth D. , Erasmus Margareth , Esterhuizen Terence , Evans Thomas , Fattore Christine , Gelderbloem Sebastian , Gempies Diann , Goliath Sandra , Gomes Peggy , Gregg Yolande , Hamilton Elizabeth , Hanekom Willem A. , Hector Johanna , Herling Roxanne , Herselman Yulandi , Hopkins Robert , Hughes Jane , Hunt Devin , Issel Henry , Janosczyk Helene , Jaxa Lungisa , Jones Carolyn , Kassiem Jateel , Keffers Sophie , Kelepu Xoliswa , Keyser Alana , Kieffer Alexia , Kromann Ingrid , Kruger Sandra , Lambrick Maureen , Landry Bernard , Langata Phumzile , Lempicki Maria , Locas Marie-Christine , Luabeya Angelique , Mactavie Lauren , Makunzi Lydia , Mangala Pamela , Maqubela Clive , Mosito Boitumelo , Mouton Angelique , Mulenga Humphrey , Mullins Mariana , Noble Julia , Nombida Onke , O’Dee Dawn , O’Neil Amy , Ockhuis Rose , Omarjee Saleha , Opperman Fajwa , Patel Dhaval , Petersen Christel , Pretorius Abraham , Pretorius Debbie , Raine Michael , Raphela Rodney , Ratangee Maigan , Rauner Christian , Rossouw Susan , Roux Surita , Rutkowski Kathryn Tucker , Ryall Robert , Schoeman Elisma , Schreuder Constance , Self Steven G. , September Cashwin , Shenje Justin , Shepherd Barbara , Siefers Heather , Sinandile Eunice , Skea Danna , Steyn Marcia , Su Jin , Sutton Sharon , Swarts Anne , Syntin Patrick , Tameris Michele , Tyambetyu Petrus , van der Merwe Arrie , van der Riet Elize , van der Vendt Dorothy , van der Westhuizen Denise , van der Westhuizen Anja , van Rooyen Elma , Veldsman Ashley , Veltdsman Helen , Vermeulen Emerencia , Matiwane Sindile Wiseman , Xoyana Noncedo 
Published: October 2020

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.