@article{a508d190221f4de4955c6cbc7cb849a4,
title = "Effects of BCG vaccination on donor unrestricted T cells in two prospective cohort studies",
abstract = "Background: Non-protein antigen classes can be presented to T cells by near-monomorphic antigen-presenting molecules such as CD1, MR1, and butyrophilin 3A1. Such T cells, referred to as donor unrestricted T (DURT) cells, typically express stereotypic T cell receptors. The near-unrestricted nature of DURT cell antigen recognition is of particular interest for vaccine development, and we sought to define the roles of DURT cells, including MR1-restricted MAIT cells, CD1b-restricted glucose monomycolate (GMM)-specific T cells, CD1d-restricted NKT cells, and γδ T cells, in vaccination against Mycobacterium tuberculosis. Methods: We compared and characterized DURT cells following primary bacille Calmette-Guerin (BCG) vaccination in a cohort of vaccinated and unvaccinated infants, as well as before and after BCG-revaccination in adults. Findings: BCG (re)vaccination did not modulate peripheral blood frequencies, T cell activation or memory profiles of MAIT cells, CD1b-restricted GMM-specific and germline-encoded mycolyl-reactive (GEM) cells or CD1d-restricted NKT cells. By contrast, primary BCG vaccination was associated with increased frequencies of γδ T cells as well as a novel subset of CD26+CD161+TRAV1-2− IFN-γ-expressing CD4+ T cells in infants. Interpretation: Our findings, that most DURT cell populations were not modulated by BCG, do not preclude a role of BCG in modulating other qualitative aspects of DURT cells. More studies are required to understand the full potential of DURT cells in new TB vaccine strategies. Funding: Aeras, the National Institutes of Health, and the Bill and Melinda Gates Foundation.",
keywords = "BCG, Memory, Tuberculosis, Unconventional T cells, Vaccination",
author = "{the Delayed BCG Study Team} and Anele Gela and Melissa Murphy and Miguel Rodo and Kate Hadley and Hanekom, {Willem A.} and Boom, {W. Henry} and Johnson, {John L.} and Hoft, {Daniel F.} and Joosten, {Simone A.} and Ottenhoff, {Tom H.M.} and Sara Suliman and Moody, {D. Branch} and Lewinsohn, {David M.} and Mark Hatherill and Chetan Seshadri and Elisa Nemes and Scriba, {Thomas J.} and Libby Briel and Hellen Veldtsman and Nondumiso Khomba and Bernadette Pienaar and Hadn Africa and Marcia Steyn",
note = "Funding Information: We would like to thank the participants who gave their time and dedication to this study. This study was initiated and designed by members of the Collaboration for TB Vaccine Discovery (CVTD), DURT Research Community, with support from the Bill and Melinda Gates Foundation. The MR1 tetramer technology was produced by the NIH Tetramer Core Facility as permitted to be distributed by the University of Melbourne. All datasets and metadata have been deposited in Zivahub (https://figshare.com/s/91b7b121ea2dcf7b5b36), an open access data repository hosted by the University of Cape Town's institutional data repository powered by Figshare for Institutions. Funding Information: The study was funded by Aeras and the Bill and Melinda Gates Foundation. The delayed BCG infant study was funded by NIH R01 grant AI087915 and the adult BCG revaccination study was funded by NIH grant NO1-AI70022. CD1b tetramers, ligands and their validation were supported by R01 AI049313. Anele Gela was supported by postdoctoral fellowships from the Claude Leon Foundation and the Harry Crossley Foundation. Melissa Murphy was supported by a Masters and Doctoral Innovation Scholarship from the National Research Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Publisher Copyright: {\textcopyright} 2022 The Authors",
year = "2022",
month = feb,
doi = "10.1016/j.ebiom.2022.103839",
language = "English (US)",
volume = "76",
journal = "EBioMedicine",
issn = "2352-3964",
publisher = "Elsevier BV",
}