{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T00:06:18Z","timestamp":1788307578564,"version":"build-2803163510"},"reference-count":65,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,6,21]],"date-time":"2024-06-21T00:00:00Z","timestamp":1718928000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100022426","name":"National Indian Health Board","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100022426","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    Tuberculosis (TB) remains a significant global health challenge, with approximately 1.5 million deaths per year. The Bacillus Calmette-Gu\u00e9rin (BCG) vaccine against TB is used in infants but shows variable protection. Here, we introduce a novel approach using a double gene knockout mutant (DKO) from wild-type\n                    <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n                    (\n                    <jats:italic>Mtb<\/jats:italic>\n                    ) targeting\n                    <jats:italic>fbpA<\/jats:italic>\n                    and\n                    <jats:italic>sapM<\/jats:italic>\n                    genes. DKO exhibited enhanced anti-TB gene expression in mouse antigen-presenting cells, activating autophagy and inflammasomes. This heightened immune response improved\n                    <jats:italic>ex vivo<\/jats:italic>\n                    antigen presentation to T cells. Subcutaneous vaccination with DKO led to increased protection against TB in wild-type C57Bl\/6 mice, surpassing the protection observed in caspase 1\/11-deficient C57Bl\/6 mice and highlighting the critical role of inflammasomes in TB protection. The DKO vaccine also generated stronger and longer-lasting protection than the BCG vaccine in C57Bl\/6 mice, expanding both CD62L\n                    <jats:sup>-<\/jats:sup>\n                    CCR7\n                    <jats:sup>-<\/jats:sup>\n                    CD44\n                    <jats:sup>+\/-<\/jats:sup>\n                    CD127\n                    <jats:sup>+<\/jats:sup>\n                    effector T cells and CD62L\n                    <jats:sup>+<\/jats:sup>\n                    CCR7\n                    <jats:sup>+\/-<\/jats:sup>\n                    CD44\n                    <jats:sup>+<\/jats:sup>\n                    CD127\n                    <jats:sup>+<\/jats:sup>\n                    central memory T cells. These immune responses correlated with a substantial \u2265 1.7-log\n                    <jats:sub>10<\/jats:sub>\n                    reduction in\n                    <jats:italic>Mtb<\/jats:italic>\n                    lung burden. The DKO vaccine represents a promising new approach for TB immunization that mediates protection through autophagy and inflammasome pathways.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2024.1321657","type":"journal-article","created":{"date-parts":[[2024,6,21]],"date-time":"2024-06-21T00:25:47Z","timestamp":1718929547000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["The \u0394fbpA\u0394sapM candidate vaccine derived from Mycobacterium tuberculosis H37Rv is markedly immunogenic in macrophages and induces robust immunity to tuberculosis in mice"],"prefix":"10.3389","volume":"15","author":[{"given":"Abhishek","family":"Mishra","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arshad","family":"Khan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vipul 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