{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T23:17:16Z","timestamp":1787008636084,"version":"build-2736575974"},"reference-count":39,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2019,8,15]],"date-time":"2019-08-15T00:00:00Z","timestamp":1565827200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"European Union\u2019s Horizon 2020","award":["TBVAC2020"],"award-info":[{"award-number":["TBVAC2020"]}]},{"name":"European Union\u2019s Horizon 2020","award":["643381"],"award-info":[{"award-number":["643381"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,6,24]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Strategies to prevent Mycobacterium tuberculosis (Mtb) infection are urgently required. In this study, we aimed to identify correlates of protection against Mtb infection.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Two groups of Mtb-exposed contacts of tuberculosis (TB) patients were recruited and classified according to their Mtb infection status using the tuberculin skin test (TST; cohort 1) or QuantiFERON (QFT; cohort 2). A negative reading at baseline with a positive reading at follow-up classified TST or QFT converters and a negative reading at both time points classified TST or QFT nonconverters. Ribonucleic acid sequencing, Mtb proteome arrays, and metabolic profiling were performed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Several genes were found to be differentially expressed at baseline between converters and nonconverters. Gene set enrichment analysis revealed a distinct B-cell gene signature in TST nonconverters compared to converters. When infection status was defined by QFT, enrichment of type I interferon was observed. A remarkable area under the curve (AUC) of 1.0 was observed for IgA reactivity to Rv0134 and an AUC of 0.98 for IgA reactivity to both Rv0629c and Rv2188c. IgG reactivity to Rv3223c resulted in an AUC of 0.96 and was markedly higher compared to TST nonconverters. We also identified several differences in metabolite profiles, including changes in biomarkers of inflammation, fatty acid metabolism, and bile acids. Pantothenate (vitamin B5) was significantly increased in TST nonconverters compared to converters at baseline (q = 0.0060).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These data provide new insights into the early protective response to Mtb infection and possible avenues to interfere with Mtb infection, including vitamin B5 supplementation.<\/jats:p>\n                    <jats:p>Analysis of blood from highly exposed household contacts from The Gambia who never develop latent Mycobacterium tuberculosis infection shows distinct transcriptomic, antibody, and metabolomic profiles compared to those who develop latent tuberculosis infection but prior to any signs of infection.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/cid\/ciz785","type":"journal-article","created":{"date-parts":[[2019,8,9]],"date-time":"2019-08-09T15:14:50Z","timestamp":1565363690000},"page":"30-40","source":"Crossref","is-referenced-by-count":30,"title":["Changes in Transcript, Metabolite, and Antibody Reactivity During the Early Protective Immune Response in Humans to Mycobacterium tuberculosis Infection"],"prefix":"10.1093","volume":"71","author":[{"given":"January","family":"Weiner","sequence":"first","affiliation":[{"name":"Max Planck Institute for Infection Biology, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa","family":"Domaszewska","sequence":"first","affiliation":[{"name":"Max Planck Institute for Infection Biology, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Donkor","sequence":"first","affiliation":[{"name":"Vaccines and Immunity Theme, Medical Research Council Unit The Gambia at the London School of Hygiene and Tropical Medicine, Banjul, The Gambia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan H E","family":"Kaufmann","sequence":"first","affiliation":[{"name":"Max Planck Institute for Infection Biology, Berlin, Germany"},{"name":"Hagler Institute for Advanced Study, Texas A&M University, College Station, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip C","family":"Hill","sequence":"first","affiliation":[{"name":"Vaccines and Immunity Theme, Medical Research Council Unit The Gambia at the London School of Hygiene and Tropical Medicine, Banjul, The Gambia"},{"name":"Otago University, Otago, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jayne S","family":"Sutherland","sequence":"first","affiliation":[{"name":"Vaccines and Immunity Theme, Medical Research Council Unit The Gambia at the London School of Hygiene and Tropical Medicine, Banjul, The Gambia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,8,15]]},"reference":[{"key":"2020062404335045500_CIT0001","author":"World Health Organization. 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