Journal article
A Functional Role for Antibodies in Tuberculosis
LL Lu, AW Chung, TR Rosebrock, M Ghebremichael, WH Yu, PS Grace, MK Schoen, F Tafesse, C Martin, V Leung, AE Mahan, M Sips, MP Kumar, J Tedesco, H Robinson, E Tkachenko, M Draghi, KJ Freedberg, H Streeck, TJ Suscovich Show all
Cell | CELL PRESS | Published : 2016
Abstract
While a third of the world carries the burden of tuberculosis, disease control has been hindered by a lack of tools, including a rapid, point-of-care diagnostic and a protective vaccine. In many infectious diseases, antibodies (Abs) are powerful biomarkers and important immune mediators. However, in Mycobacterium tuberculosis (Mtb) infection, a discriminatory or protective role for humoral immunity remains unclear. Using an unbiased antibody profiling approach, we show that individuals with latent tuberculosis infection (Ltb) and active tuberculosis disease (Atb) have distinct Mtb-specific humoral responses, such that Ltb infection is associated with unique Ab Fc functional profiles, selecti..
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Awarded by Ragon Institute of MGH, MIT and Harvard
Funding Acknowledgements
CEM.NKR-CCR5 was obtained through the AIDS Research and Reference Reagent Program, Division of AIDS, NIAID, NIH. The following reagents were obtained through BEI Resources, NIAID, NIH: cell membrane, culture filtrate, cytosol protein, soluble cell wall protein, and soluble protein fractions of H37RV M. tuberculosis. We thank Peter Sorger for access to the Operetta High-Content Imaging Fluorescence Microscope; Rebecca Gelman, Director of the Harvard Center for AIDS Biostatistics Core, for her advice; and many additional members of the SATVI team who helped with enrollment and evaluation of participants. This work was supported by the NIH (grants R01 AI080289 and AI102660, to G.A.), Dr. Dan Wattendorf and DARPA BAA-11-65 (G.A.), Harvard University Center for AIDS Research (CFAR) grant P30 AI060354 (to G.A., S.M.F., T.R., and M.G., Ragon BL3 and Imaging Core Facility), grant T32 AI007387 (to L.L.L.), NHMRC APP1036470 (A.W.C.), Bill and Melinda Gates Foundation CAVD (OPP1032817: Leveraging Antibody Effector Function) (G.A.), the Pozen Family Foundation (S.M.F.), the Doris Duke Medical Research Foundation (S.M.F.), the Burroughs Wellcome Foundation (S.M.F.), and the Ragon Institute of MGH, MIT, and Harvard.