{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T13:06:48Z","timestamp":1782997608699,"version":"3.54.5"},"reference-count":39,"publisher":"American Society for Microbiology","issue":"7","license":[{"start":{"date-parts":[[2016,7,1]],"date-time":"2016-07-01T00:00:00Z","timestamp":1467331200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Clin Vaccine Immunol"],"published-print":{"date-parts":[[2016,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Earlier studies aimed at defining protective immunity induced by\n            <jats:named-content content-type=\"genus-species\">Mycobacterium bovis<\/jats:named-content>\n            BCG immunization have largely focused on the induction of antituberculosis CD4\n            <jats:sup>+<\/jats:sup>\n            and CD8\n            <jats:sup>+<\/jats:sup>\n            T cell responses. Here we describe a vaccine consisting of a BCG\u0394\n            <jats:italic>mmaA4<\/jats:italic>\n            deletion mutant formulated in dimethyl dioctadecyl-ammonium bromide (DDA) with\n            <jats:sc>d<\/jats:sc>\n            -(+)-trehalose 6,6\u2032-dibehenate (TDB) (DDA\/TDB) adjuvant (A4\/Adj) that protected TCR\u03b4\n            <jats:sup>\u2212\/\u2212<\/jats:sup>\n            mice depleted of CD4\n            <jats:sup>+<\/jats:sup>\n            , CD8\n            <jats:sup>+<\/jats:sup>\n            , and NK1.1\n            <jats:sup>+<\/jats:sup>\n            T cells against an aerosol challenge with\n            <jats:named-content content-type=\"genus-species\">M. tuberculosis<\/jats:named-content>\n            . These mice were significantly protected relative to mice immunized with a nonadjuvanted BCG\u0394\n            <jats:italic>mmaA4<\/jats:italic>\n            (BCG-A4) mutant and nonvaccinated controls at 2 months and 9 months postvaccination. In the absence of all T cells following treatment with anti-Thy1.2 antibody, the immunized mice lost the ability to control the infection. These results indicate that an unconventional T cell population was mediating protection in the absence of CD4\n            <jats:sup>+<\/jats:sup>\n            , CD8\n            <jats:sup>+<\/jats:sup>\n            , NK1.1\n            <jats:sup>+<\/jats:sup>\n            , and TCR\u03b3\u03b4 T cells and could exhibit memory. Focusing on CD4\n            <jats:sup>\u2212<\/jats:sup>\n            CD8\n            <jats:sup>\u2212<\/jats:sup>\n            double-negative (DN) T cells, we found that these cells accumulated in the lungs postchallenge significantly more in A4\/Adj-immunized mice and induced significantly greater frequencies of pulmonary gamma interferon (IFN-\u03b3)-producing cells than were seen in the nonvaccinated or nonadjuvanted BCG control groups. Moreover, pulmonary DN T cells from the A4\/Adj group exhibited significantly higher IFN-\u03b3 integrated median fluorescence intensity (iMFI) values than were seen in the control groups. We also showed that enriched DN T cells from mice immunized with A4\/Adj could control mycobacterial growth\n            <jats:italic>in vitro<\/jats:italic>\n            significantly better than naive whole-spleen cells. These results suggest that formulating BCG in DDA\/TDB adjuvant confers superior protection in immunocompromised mice and likely involves the induction of long-lived memory DN T cells.\n          <\/jats:p>","DOI":"10.1128\/cvi.00232-16","type":"journal-article","created":{"date-parts":[[2016,5,26]],"date-time":"2016-05-26T03:35:15Z","timestamp":1464233715000},"page":"638-647","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":6,"title":["Induction of Unconventional T Cells by a Mutant Mycobacterium bovis BCG Strain Formulated in Cationic Liposomes Correlates with Protection against Mycobacterium tuberculosis Infections of Immunocompromised Mice"],"prefix":"10.1128","volume":"23","author":[{"given":"Steven C.","family":"Derrick","sequence":"first","affiliation":[{"name":"Center for Biologics Evaluation and Research, United States Food and Drug Administration, Silver Spring, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Idalia","family":"Yabe","sequence":"additional","affiliation":[{"name":"National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheldon","family":"Morris","sequence":"additional","affiliation":[{"name":"Center for Biologics Evaluation and Research, United States Food and Drug Administration, Silver Spring, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siobhan","family":"Cowley","sequence":"additional","affiliation":[{"name":"Center for Biologics Evaluation and Research, United States Food and Drug Administration, Silver Spring, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_1_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.micpath.2012.12.002"},{"key":"e_1_3_1_3_2","volume-title":"Tuberculosis fact sheet no. 104","author":"World Health Organization","year":"2015","unstructured":"World Health Organization. 2015. Tuberculosis fact sheet no. 104. World Health Organization, Geneva, Switzerland. http:\/\/www.who.int\/mediacentre\/factsheets\/fs104\/en."},{"key":"e_1_3_1_4_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.med.60.053107.103955"},{"key":"e_1_3_1_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/22.6.1154"},{"key":"e_1_3_1_6_2","doi-asserted-by":"publisher","DOI":"10.1080\/003655401300077144"},{"key":"e_1_3_1_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.73.3.1903-1905.2005"},{"key":"e_1_3_1_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2005.01.150"},{"key":"e_1_3_1_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2005.11.017"},{"key":"e_1_3_1_10_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.178.6.3721"},{"key":"e_1_3_1_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00052-08"},{"key":"e_1_3_1_12_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0032959"},{"key":"e_1_3_1_13_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000081"},{"key":"e_1_3_1_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2006.05.097"},{"key":"e_1_3_1_15_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2567.2006.02491.x"},{"key":"e_1_3_1_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2011.02.010"},{"key":"e_1_3_1_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2009.10.047"},{"key":"e_1_3_1_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/CVI.00359-08"},{"key":"e_1_3_1_19_2","doi-asserted-by":"crossref","first-page":"6","DOI":"10.3389\/fimmu.2013.00006","article-title":"Immunoregulatory CD4(-)CD8(-) T cells as a potential therapeutic tool for transplantation, autoimmunity, and cancer","volume":"4","author":"Hillhouse EE","year":"2013","unstructured":"Hillhouse EE, Delisle JS, Lesage S. 2013. Immunoregulatory CD4(-)CD8(-) T cells as a potential therapeutic tool for transplantation, autoimmunity, and cancer. Front Immunol 4:6.","journal-title":"Front Immunol"},{"key":"e_1_3_1_20_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20050569"},{"key":"e_1_3_1_21_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.276.5319.1684"},{"key":"e_1_3_1_22_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0050923"},{"key":"e_1_3_1_23_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0077334"},{"key":"e_1_3_1_24_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1004396"},{"key":"e_1_3_1_25_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1003441"},{"key":"e_1_3_1_26_2","doi-asserted-by":"publisher","DOI":"10.1159\/000076526"},{"key":"e_1_3_1_27_2","doi-asserted-by":"publisher","DOI":"10.1089\/088922201750290096"},{"key":"e_1_3_1_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/0090-1229(89)90033-0"},{"key":"e_1_3_1_29_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/174.5.969"},{"key":"e_1_3_1_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2010.03.027"},{"key":"e_1_3_1_31_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri979"},{"key":"e_1_3_1_32_2","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.5RI0315-096R"},{"key":"e_1_3_1_33_2","doi-asserted-by":"publisher","DOI":"10.1111\/joim.12449"},{"key":"e_1_3_1_34_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0066115"},{"key":"e_1_3_1_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2014.11.004"},{"key":"e_1_3_1_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tube.2010.06.002"},{"key":"e_1_3_1_37_2","doi-asserted-by":"publisher","DOI":"10.1128\/CVI.00718-14"},{"key":"e_1_3_1_38_2","doi-asserted-by":"publisher","DOI":"10.1128\/CVI.00271-15"},{"key":"e_1_3_1_39_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-014-1243-1"},{"key":"e_1_3_1_40_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-01-329656"}],"container-title":["Clinical and Vaccine Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/CVI.00232-16","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/CVI.00232-16","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,7,29]],"date-time":"2021-07-29T20:51:52Z","timestamp":1627591912000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/CVI.00232-16"}},"subtitle":[],"editor":[{"given":"D. W.","family":"Pascual","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2016,7]]},"references-count":39,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2016,7]]}},"alternative-id":["10.1128\/CVI.00232-16"],"URL":"https:\/\/doi.org\/10.1128\/cvi.00232-16","relation":{},"ISSN":["1556-6811","1556-679X"],"issn-type":[{"value":"1556-6811","type":"print"},{"value":"1556-679X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,7]]},"assertion":[{"value":"2016-05-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-05-18","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-07-05","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}