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However, the schedule of subunit vaccine boosting is not well investigated, especially the optimal immune responses and vaccine immunization schedules are still not clear. We have constructed a novel subunit vaccine candidate consisting of fusion protein Ag85B\u2010Mpt64 (190\u2010198)\u2010Mtb8.4 (AMM) in a complex adjuvant composed of dimo\u2010thylidioctyl ammonium bromide (DDA) and BCG polysaccharide nucleic acid (BCG\u2010PSN). In this study, we compared the effect of different boosting schedules of the subunit vaccine in the prime\u2010boost strategies. C57BL\/6 mice were primed with BCG first and then boosted with the AMM vaccine once at 10th week, twice at 8th, 10th week, or thrice at 6th, 8th, 10th week, respectively. The immune responses were evaluated at the 14th and 20th weeks, respectively. Twelve weeks after the last immunization, the mice were challenged with virulent <jats:italic>Mycobacterium tuberculosis<\/jats:italic> strain H37Rv, and the protective effect was evaluated. The results showed that BCG priming and the AMM vaccine boosting twice induced the strongest antigen\u2010specific IFN\u2010\u03b3 and IL\u20102 production, down\u2010regulated CD4<jats:sup>+<\/jats:sup>\u2003CD25<jats:sup>+<\/jats:sup>\u2003FoxP3<jats:sup>+<\/jats:sup> regulatory T cells (Tregs) and had the best protective effect among all groups, while boosting thrice induced the strongest IL\u20104 production and did not improve BCG\u2010primed protection significantly. Boosting BCG with the AMM vaccine twice instead of once or thrice induced strong Th1\u2010type immunity and down\u2010regulated Tregs significantly, which correlated with the best protection against <jats:italic>M.\u00a0tuberculosis<\/jats:italic> infection in mice.<\/jats:p>","DOI":"10.1111\/j.1365-3083.2011.02666.x","type":"journal-article","created":{"date-parts":[[2011,11,26]],"date-time":"2011-11-26T00:05:13Z","timestamp":1322265913000},"page":"293-300","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Subunit Vaccine Candidate AMM Down\u2010Regulated the Regulatory T Cells and Enhanced the Protective Immunity of BCG on a Suitable 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