{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:16:47Z","timestamp":1790295407594,"version":"4.1.0"},"reference-count":83,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T00:00:00Z","timestamp":1649721600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Boosting Bacillus Calmette-Gu\u00e9rin (BCG) with subunit vaccine is expected to induce long-term protection against tuberculosis (TB). However, it is urgently needed to optimize the boosting schedule of subunit vaccines, which consists of antigens from or not from BCG, to induce long-term immune memory. To address it two subunit vaccines, Mtb10.4-HspX (MH) consisting of BCG antigens and ESAT6-CFP10 (EC) consisting of antigens from the region of difference (RD) of <jats:italic>Mycobacterium tuberculosis<\/jats:italic> (<jats:italic>M. tuberculosis<\/jats:italic>), were applied to immunize BCG-primed C57BL\/6 mice twice or thrice with different intervals, respectively. The long-term antigen-specific immune responses and protective efficacy against <jats:italic>M. tuberculosis<\/jats:italic> H37Ra were determined. The results showed that following BCG priming, MH boosting twice at 12-24 weeks or EC immunizations thrice at 12-16-24 weeks enhanced the number and function of long-lived memory T cells with improved protection against H37Ra, while MH boosting thrice at 12-16-24 weeks or twice at 8-14 weeks and EC immunizations twice at 12-24 weeks or thrice at 8-10-14 weeks didn\u2019t induce long-term immunity. It suggests that following BCG priming, both BCG antigens MH boosting twice and \u201cnon-BCG\u201d antigens EC immunizations thrice at suitable intervals induce long-lived memory T cell-mediated immunity.<\/jats:p>","DOI":"10.3389\/fimmu.2022.862726","type":"journal-article","created":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T05:16:35Z","timestamp":1649740595000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["Optimizing the Boosting Schedule of Subunit Vaccines Consisting of BCG and \u201cNon-BCG\u201d Antigens to Induce Long-Term Immune 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