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The use of live bacterial vectors to express the recombinant antigen in vivo will obviate the need for large\u2010scale purification of recombinant protein and may also augment the efficacy of oral tolerance induction.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aim<\/jats:title><jats:p>The objective of the study was to explore the use of recombinant <jats:italic>Mycobacterium smegmatis<\/jats:italic> as a live vector for oral delivery of antigens to induce immune tolerance.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method and Results<\/jats:title><jats:p>We developed a <jats:italic>M.\u00a0smegmatis<\/jats:italic> vector to secrete a recombinant tripeptide construct (<jats:styled-content style=\"fixed-case\">AHC<\/jats:styled-content>; peptides from Apolipoprotein B, Heat\u2010shock protein 60 and <jats:italic>Chlamydia pneumoniae<\/jats:italic> outer membrane protein) expressed in a dendroaspin protein scaffold in <jats:styled-content style=\"fixed-case\">pJH<\/jats:styled-content>154 background. Immune response and oral tolerance to the cloned peptides were studied in C57\/<jats:styled-content style=\"fixed-case\">BL<\/jats:styled-content>6 mice. The efficacy of this live vaccine to control atherosclerosis was studied in ApoE<jats:sup>\u2212\/\u2212<\/jats:sup> knockout mice in C57\/<jats:styled-content style=\"fixed-case\">BL<\/jats:styled-content>6 background. Oral administration of <jats:italic>M.\u00a0smegmatis<\/jats:italic> secreting the cloned <jats:styled-content style=\"fixed-case\">AHC<\/jats:styled-content> antigen was found to induce tolerance to cloned protein and reduce the development of atherosclerosis by 24.0% compared to control<jats:bold>.<\/jats:bold> Protection against atherosclerosis was associated with increase in expression of regulatory T cell\u2010associated markers including <jats:styled-content style=\"fixed-case\">CTLA<\/jats:styled-content>4 (1.8\u2010fold), Foxp3 (2.6\u2010fold), <jats:styled-content style=\"fixed-case\">TGF<\/jats:styled-content>\u2010\u03b2 (2.8\u2010fold), <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>10 (2.9\u2010fold), and reduction in lipids, macrophage infiltration, and expression of inflammatory mediators in aorta.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our results suggest that <jats:italic>M.\u00a0smegmatis<\/jats:italic> can be developed as an oral carrier of recombinant proteins to treat inflammatory autoimmune diseases.<\/jats:p><\/jats:sec>","DOI":"10.1111\/1755-5922.12201","type":"journal-article","created":{"date-parts":[[2016,5,31]],"date-time":"2016-05-31T06:42:55Z","timestamp":1464676975000},"page":"314-324","source":"Crossref","is-referenced-by-count":5,"title":["Oral administration of recombinant <i>Mycobacterium smegmatis<\/i> expressing a tripeptide construct derived from endogenous and microbial antigens prevents atherosclerosis in ApoE<sup>\u2212\/\u2212<\/sup> mice"],"prefix":"10.1111","volume":"34","author":[{"given":"Vrushali","family":"Deshpande","sequence":"first","affiliation":[{"name":"Molecular Immunology Thrombosis Research Institute  Bangalore India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rameshkumar","family":"Krishnan","sequence":"additional","affiliation":[{"name":"Molecular Immunology Thrombosis Research Institute  Bangalore 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